Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Vasoconstriction”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 415 records · Page 23Linked to original sources

The effect of pyrogen administration on sweating and vasoconstriction thresholds during desflurane anesthesia.

BACKGROUND: General anesthetics increase the sweating-to-vasoconstriction interthreshold range (temperatures not triggering thermoregulatory defenses), whereas fever is believed to only increase the setpoint (target core temperature). However, no data characterize thresholds (temperatures triggering thermoregulatory defenses) during combined anesthesia and fever. Most likely, the combination produces an expanded interthreshold range around an elevated setpoint. The authors therefore tested the hypothesis that thermoregulatory response thresholds during the combination of fever and anesthesia are simply the linear combination of the thresholds resulting from each intervention alone. METHODS: The authors studied eight healthy male volunteers. Fever was induced on the appropriate days by intravenous injection of 30 IU/g human recombinant interleukin 2 (IL-2), followed 2 h later by an additional 70 IU/g. General anesthesia consisted of desflurane 0.6 minimum alveolar concentration (MAC). The volunteers were randomly assigned to the following groups: (1) control (no desflurane, no IL-2); (2) IL-2 alone; (3) desflurane alone; and (4) desflurane plus IL-2. During the fever plateau, volunteers were warmed until sweating was observed and then cooled to vasoconstriction. Sweating was evaluated from a ventilated capsule and vasoconstriction was quantified by volume plethysmography. The tympanic membrane temperatures triggering significant sweating and vasoconstriction identified the respective response thresholds. Data are presented as the mean +/- SD; P < 0.05 was considered significant. RESULTS: The interthreshold range was near 0.40 degrees C on both the control day and during IL-2 administration alone. On the IL-2 alone day, however, the interthreshold range was shifted to higher temperatures. The interthreshold range increased significantly during desflurane anesthesia to 1.9+/-0.6 degrees C. The interthreshold range during the combination of desflurane and IL-2 was 1.2+/-0.6 degrees C, which was significantly greater than on the control and IL-2 alone days. However, it was also significantly less than during desflurane alone. CONCLUSION: The combination of desflurane and IL-2 caused less thermoregulatory inhibition than would be expected based on the effects of either treatment alone. Fever-induced activation of the sympathetic nervous system may contribute by compensating for a fraction of the anesthetic-induced thermoregulatory impairment.

Adult↗

Fructose administration increases intraoperative core temperature by augmenting both metabolic rate and the vasoconstriction threshold.

BACKGROUND: The authors tested the hypothesis that intravenous fructose ameliorates intraoperative hypothermia both by increasing metabolic rate and the vasoconstriction threshold (triggering core temperature). METHODS: Forty patients scheduled to undergo open abdominal surgery were divided into two equal groups and randomly assigned to intravenous fructose infusion (0.5 g . kg(-1) . h(-1) for 4 h, starting 3 h before induction of anesthesia and continuing for 4 h) or an equal volume of saline. Each treatment group was subdivided: Esophageal core temperature, thermoregulatory vasoconstriction, and plasma concentrations were determined in half, and oxygen consumption was determined in the remainder. Patients were monitored for 3 h after induction of anesthesia. RESULTS: Patient characteristics, anesthetic management, and circulatory data were similar in the four groups. Mean final core temperature (3 h after induction of anesthesia) was 35.7 degrees +/- 0.4 degrees C (mean +/- SD) in the fructose group and 35.1 degrees +/- 0.4 degrees C in the saline group (P = 0.001). The vasoconstriction threshold was greater in the fructose group (36.2 degrees +/- 0.3 degrees C) than in the saline group (35.6 degrees +/- 0.3 degrees C; P < 0.001). Oxygen consumption immediately before anesthesia induction in the fructose group (214 +/- 18 ml/min) was significantly greater than in the saline group (181 +/- 8 ml/min; P < 0.001). Oxygen consumption was 4.0 l greater in the fructose patients during 3 h of anesthesia; the predicted difference in mean body temperature based only on the difference in metabolic rates was thus only 0.4 degrees C. Epinephrine, norepinephrine, and angiotensin II concentrations and plasma renin activity were similar in each treatment group. CONCLUSIONS: Preoperative fructose infusion helped to maintain normothermia by augmenting both metabolic heat production and increasing the vasoconstriction threshold.

Adult↗

Importance of hypoxic vasoconstriction in maintaining oxygenation during acute lung injury.

OBJECTIVE: To investigate the role of hypoxic pulmonary vasoconstriction in the intrapulmonary blood flow redistribution and gas exchange protection during oleic acid acute lung injury. DESIGN: Prospective, controlled animal study. SETTING: Research laboratory of an academic institution. SUBJECTS: Three groups of five mongrel dogs. INTERVENTIONS: Induction of acute lung injury by 0.08 mL/kg oleic acid intravenously. Hypoxic pulmonary vasoconstriction inhibition by Escherichia coli endotoxin microdose (15 microg/kg) pretreatment or by metabolic alkalosis (pH 7.60). MEASUREMENTS AND MAIN RESULTS: Pulmonary arterial and venous resistances were determined by flow-pressure curves and by capillary pressure estimation. Regional lung water and pulmonary blood flow were assessed by positron emission tomography. Oleic acid alone increased the arterial and venous resistances, redistributed blood flow away from edematous areas, and decreased the Pao2 from 507 +/- 16 to 373 +/- 60 torr. on Fio2 1.0 and positive end-expiratory pressure 5 cm H2O. Endotoxin pretreatment inhibited the increase in arterial resistance, suppressed the redistribution, and decreased the Pao2 to 105 +/- 22 torr. Alkalosis inhibited the increase in arterial and venous resistances, suppressed the redistribution, and decreased the Pao2 to 63 +/- 12 torr. Reversal of the alkalosis increased the arterial and venous resistances, restored the perfusion redistribution, and improved the Pao2 to 372 +/- 63 torr. Changes in blood gases conformed to predictions of a computer lung model in which hypoxic pulmonary vasoconstriction was suppressed by endotoxin and alkalosis. CONCLUSIONS: We conclude that in oleic acid-induced lung injury, a) pulmonary hypertension results from increases in both arterial and venous resistances; b) the increase in arterial resistance is the primary mechanism responsible for the perfusion redistribution and the gas exchange protection; and c) the increase in arterial resistance is most consistent with hypoxic pulmonary vasoconstriction.

Animals↗

Alveolar mechanics alter hypoxic pulmonary vasoconstriction.

OBJECTIVES: Hypoxic pulmonary vasoconstriction is the primary physiologic mechanism that maintains a proper ventilation/perfusion match, but it fails in diffuse lung injuries such as acute respiratory distress syndrome. Acute respiratory distress syndrome is associated with pulmonary surfactant loss that alters alveolar mechanics (i.e., dynamic change in alveolar size and shape during ventilation), converting normal stable alveoli into unstable alveoli. We hypothesized that alveolar instability stents open pulmonary microvessels and is the mechanism of hypoxic pulmonary vasoconstriction failure associated with acute respiratory distress syndrome. DESIGN: Prospective, randomized, controlled study. SETTING: University research laboratory. SUBJECTS: Ten adult pigs. INTERVENTIONS: Anesthetized ventilated pigs were prepared surgically for hemodynamic monitoring and were subjected to a right thoracotomy. An in vivo microscope was attached to the right lung, and the microvascular response to hypoxia (F(IO(2)), 15%) was measured in a lung with normal stable alveoli and in a lung with unstable alveoli caused by surfactant deactivation (Tween lavage). MEASUREMENTS AND MAIN RESULTS: Alveolar instability, defined as the difference between alveolar area at peak inspiration and end expiration and assessed as a percentage change (I-E Delta%), was significantly increased after Tween (23.9 +/- 3.0, I-E Delta%) compared with baseline (2.4 +/- 1.0, I-E Delta%). Alveolar instability was associated with the following microvascular changes: a) increased vasoconstriction (Tween, 14.9 +/- 1.0%) in response to hypoxia compared with baseline (10.8 +/- 1.2%, p <.05); and b) increased mean vascular diameter (Tween, 41.2 +/- 1.5 microm) compared with the mean diameter at baseline (24.6 +/- 1.0 microm, p <.05). CONCLUSION: Unstable alveoli stent open pulmonary vessels, which may explain the failure of hypoxic pulmonary vasoconstriction in acute respiratory distress syndrome.

Animals↗

Cyclosporin-induced renal vasoconstriction is augmented by frusemide and by angiotensin II in humans.

OBJECTIVE: To investigate the role of the renin-angiotensin-aldosterone system as a homoeostatic mechanism by examining whether mild activation of the renin-angiotensin-aldosterone system could enhance cyclosporin-induced renal vasoconstriction and hypertension. METHODS: We artificially activated the renin-angiotensin-aldosterone system by two means: by pretreatment with frusemide (40 mg/day orally for 2 days) and by administering exogenous angiotensin II (1 ng/kg per min intravenously). In both cases the levels of renin-angiotensin-aldosterone system activation achieved did not by themselves alter renal blood flow, glomerular filtration rate or blood pressure. We then examined the effect of cyclosporin (10 mg/kg twice a day orally) in the presence of the activated renin-angiotensin-aldosterone system in normal humans. RESULTS: Cyclosporin alone acutely altered neither glomerular filtration rate (760 versus 734ml, NS; area under the curve for placebo versus cyclosporin) nor effective renal plasma flow (4,163 versus 3,915 ml, NS; area under the curve for placebo versus cyclosporin). Co-administration of exogenous angiotensin II with cyclosporin induced a fall in effective renal plasma flow from baseline but no change in glomerular filtration rate. Frusemide pretreatment together with cyclosporin administration induced a fall in glomerular filtration rate and a fall in effective renal plasma flow. Neither exogenous angiotensin II nor frusemide pretreatment influenced the blood pressure rise induced by cyclosporin. The present findings demonstrate that renin-angiotensin-aldosterone system activation augments cyclosporin-induced renal vasoconstriction but not cyclosporin-induced systemic vasoconstriction. We suggest that the renin-angiotensin-aldosterone system suppression, which normally occurs with cyclosporin, may be a homoeostatic mechanism to help prevent cyclosporin-induced renal vasoconstriction. The renin-angiotensin-aldosterone system appears, however, to play little or no role in mediating or preventing the initial increase in blood pressure caused by cyclosporin. Furthermore, frusemide is commonly prescribed together with cyclosporin even though this combination has the potential to cause a marked increase in renal dysfunction.

Adult↗

Estrogen improves abnormal norepinephrine-induced vasoconstriction in postmenopausal women.

OBJECTIVE: An exaggerated blood pressure response to mental stress in postmenopausal women has been reported but the underlying mechanism is not clear. In the present study, we examined the role of estrogen in the blood pressure response to mental stress. SUBJECTS AND METHODS: Hemodynamic responses to mental stress and constrictor responses to norepinephrine were compared in 18 premenopausal (mean +/- SD age 33 +/- 5 years), 22 postmenopausal women (62 +/- 7 years) and 13 postmenopausal women with estrogen replacement therapy (58 +/- 8 years). Premarin was infused in 10 postmenopausal women to determine whether estrogen attenuates norepinephrine-induced vasoconstriction. The hemodynamic responses to a standard mental arithmetic test were measured. Norepinephrine (12.5, 25, 50, 100 ng/min) was infused at 0.5 ml/min for 5 min via the dorsal hand vein. Norepinephrine (100 ng/min) combined with premarin (200 microg/min) was infused into the dorsal hand vein of postmenopausal women. Changes in venous diameter were measured by ultrasonography using a 7.5 MHz transducer. RESULTS: All study subjects were healthy, normotensive and had normal lipid profiles. The postmenopausal women showed a significantly greater blood pressure response to the mental arithmetic test than the premenopausal women or those taking estrogen replacement therapy (P < 0.01). Norepinephrine induced significant dose-dependent vasoconstriction in all three groups (P < 0.001). The postmenopausal women showed significantly greater constriction in response to norepinephrine than the premenopausal women and those taking estrogen replacement therapy (P = 0.02). Premarin significantly attenuated the norepinephrine-induced vasoconstriction in the postmenopausal women (P< 0.001). CONCLUSION: Healthy, normotensive postmenopausal women showed an exaggerated blood pressure response to mental stress. An increased vasoconstriction in response to norepinephrine and loss of estrogen-mediated vasodilation may contribute to the increased blood pressure response to stress in postmenopausal women without estrogen replacement therapy.

Adult↗

Interaction between beta 2-adrenoceptor-mediated vasodilation and alpha 1-adrenoceptor-mediated vasoconstriction in the pithed normotensive rat.

With pithed normotensive rats we studied the interaction between beta 2-adrenoceptor-mediated vasodilation and alpha 1-adrenoceptor-mediated vasoconstriction. The selective beta 2-adrenoceptor agonist salbutamol was used to elicit vasodilatation. To induce alpha 1-adrenoceptor-mediated vasoconstriction, the selective alpha 1-adrenoceptor agonists cirazoline, St 587, and methoxamine were used. Furthermore, the alpha 1-adrenoceptor-mediated vasopressor effects of intravenously administered (--)-norepinephrine, and (--)-norepinephrine released from neurons by the nicotinic agonist 1,1-dimethyl-4-phenylpiperazine iodide (DMPP), the muscarinic ganglionic stimulant McN-A-343, electrical stimulation of the spinal cord, and the indirect sympathomimetic agent tyramine, were studied. By using the selective beta 2-adrenoceptor antagonist ICI 118,551, the interaction between the alpha 1-adrenoceptor-mediated vasoconstriction of (--)-epinephrine and alpha-methylnorepinephrine with their intrinsic beta 2-adrenoceptor agonistic effects was investigated. Two types of interaction between alpha 1-and beta 2-adrenoceptor-mediated vascular effects were found. Cirazoline and McN-A-343 activated alpha 1-adrenoceptors, inducing a vasoconstriction not affected by beta 2-adrenoceptor-mediated vasodilation. However, methoxamine at low doses, St 487, DMPP, electrical stimulation, intravenously administered (--)-norepinephrine, (--)-epinephrine, and alpha-methylnorepinephrine activated alpha 1-adrenoceptors, and their effect was attenuated by vasodilation. At low doses, tyramine stimulated alpha 1-adrenoceptors that were not sensitive to beta 2-adrenoceptor-mediated vasodilation, in contrast to the population of alpha 1-adrenoceptors activated at high doses of tyramine. It is hypothesized that there exist two different populations of alpha 1-adrenoceptors.

Adrenergic alpha-Agonists↗

BQ123, an ETA receptor antagonist, attenuates endothelin-1-induced vasoconstriction in rat pulmonary circulation.

Endothelin-1 (ET-1) is a potent endogenous vasoactive peptide whose role in regulation of vascular tone is unclear. BQ123 is a recently described ETA receptor antagonist which may be useful in further investigation of the physiologic and pathophysiologic significance of ET-1. To test its efficacy in the pulmonary circulation, the vascular response to exogenous ET-1 with and without BQ123 was assessed in rat pulmonary artery (PA) rings and salt-perfused lungs. In both main and distal (250-350 microns ID) PA rings, BQ123 significantly attenuated ET-1-induced contractility, but was more effective in the larger vessels. Likewise, BQ123 significantly blunted ET-1-induced vasoconstriction in perfused lungs by > 80%. In addition, it had no effect on ET-3-mediated or U46619-mediated vasoconstriction, nor did it influence ET-1-induced vasodilation. Development of ET-1-associated hydrostatic edema was also unaffected by BQ123. We conclude that BQ123 effectively attenuates ET-1-induced vasoconstriction in both PA rings and in isolated perfused lungs. The absence of effect of BQ123 on ET-3 vasoconstriction, ET-1 vasodilation, or ET-1- and ET-3-induced hydrostatic edema formation suggests that these processes may be transduced through a non-ETA receptor.

Amino Acid Sequence↗

Tetramethylpyrazine, a Chinese drug, blocks coronary vasoconstriction by endothelin-1 and decreases plasma endothelin-1 levels in experimental animals.

The purpose of this study was to investigate effects of tetramethylpyrazine (TMP), a Chinese plant-derived medicine, on coronary vasoconstriction and related electrocardiographic and histologic changes caused by endothelin-1 (ET-1), and on plasma ET-1 levels. ET-1 (75 pmol) was administered into the left coronary artery (LCA) in anesthetized closed-chest dogs with and without prior infusion of TMP (80 mg/kg). Coronary arterial diameter (CAD) was determined by coronary arteriography (CAG). Blood pressure and electrocardiogram (ECG) were monitored continuously. Histologic damage in tissues was ascertained microscopically. Plasma ET-1 and 6-keto-PGF1 levels were determined by RIA 90 min after i.v. injection of TMP (25 mg/kg; n = 5) in rabbits. Intracoronary injection of ET-1 resulted in a significant vasoconstriction of the entire vascular bed of the LCA, with a decrease in CAD of 35.9 +/- 5.7% (n = 5; p < 0.01) and ischemic changes on ECG and in tissues of endocardium, myocardium, coronary endothelial cells, and capillary vessels. Pretreatment with TMP produced a significant increase in CAD by 38.5 +/- 7.8% (n = 5; p < 0.01) and greatly suppressed the vasoconstriction produced by ET-1. The myocardial tissue damage estimated from the ratio of ischemic area for the entire area after ET-1 injection (35.6%) was completely abolished by TMP (0.6%). In addition, TMP injection induced a significant decrease in plasma ET-1 levels and an increase in 6-keto-PGF1 levels in rabbits. The Chinese medicine TMP could be a useful therapeutic agent in ischemic heart disease by suppressing coronary vasoconstriction and ischemic changes in the tissues produced by ET-1.

6-Ketoprostaglandin F1 alpha↗

ERK1/2-mediated vasoconstriction normalizes wall stress in small mesenteric arteries during NOS inhibition in vivo.

As in essential hypertension, chronic nitric-oxide synthase (NOS) inhibition leads to hypertrophic remodeling in conduit and muscular arteries and inward eutrophic remodeling in small resistance arteries with activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) in both vessel types. The authors tested the hypothesis that this remodeling heterogeneity could be related to distinct vasoreactivity patterns in small and larger arteries, with a vessel-specific function of ERK1/2 signaling. Using intravital microscopy in rats we have demonstrated that acute NOS inhibition (l-NA injection, 100 mg/kg) produced vasoconstriction of small mesenteric arteries. Consequently, the calculated in vivo wall stress was not significantly modified, despite the local rise in pressure. This could explain the lack of vascular protein synthesis elevation in vivo, an early index of hypertrophy. Inhibition of ERK1/2 activation with PD98059 blunted mesenteric artery contractions. Femoral arteries did not contract and were thus submitted to an enhanced wall stress and underwent hypertrophic remodeling in chronic conditions. In conclusion, the heterogeneous vascular remodeling in the l-NAME model is associated with a heterogeneous vasoconstriction response to acute NOS inhibition. Indeed, in contrast to larger arteries, l-NA-induced vasoconstriction in small arteries normalized wall stress and prevented early signs of hypertrophy. The results also suggest that ERK1/2 is a signaling element in NOS inhibition-induced vasoconstriction of small arteries in vivo.

Animals↗

Acute vasoconstriction after subarachnoid hemorrhage.

OBJECTIVE: Decreased cerebral blood flow (CBF) and cerebral ischemia occurring immediately after subarachnoid hemorrhage (SAH) may be caused by acute microvascular constriction. However, CBF can also be influenced by changes in intracranial pressure (ICP) and cerebral perfusion pressure (CPP). The goal of these experiments was to assess the significance of acute vasoconstriction after SAH and its relationship to changes in CBF, ICP, CPP, and extracellular glutamate concentrations. METHODS: Three experiments were performed using the endovascular filament technique to produce SAH. In the first experiment, CBF, ICP, and CPP were measured for 60 minutes after SAH (n = 21) and were correlated with the 24-hour mortality rate. In the second experiment, rats undergoing SAH (n = 23) or a sham procedure (n = 7) were perfused 60 minutes after SAH for measurement of the circumference and wall thickness of the internal carotid and anterior cerebral arteries and correlation with CBF, ICP, and CPP. In the third experiment (n = 11), extracellular glutamate concentrations determined by hippocampal and cortical microdialysis and high performance liquid chromatography were correlated with physiological changes. RESULTS: CBF reductions to less than 40% of baseline for 60 minutes after SAH predicted 24-hour mortality with 100% accuracy and were used to define "lethal" SAH. In contrast, ICP and CPP 60 minutes after SAH were not correlated with the mortality rate. The vascular circumference was significantly smaller in lethal than in sublethal SAH or sham-operated rats (P < 0.001). Vessel measurements were correlated with both CBF and hemorrhage size (P < 0.01). Extracellular glutamate concentration increased to 600% of baseline after lethal SAH in both hippocampus and cortex and was inversely correlated with CBF (r = 0.9, P < 0.001) but did not increase after sublethal SAH. CONCLUSION: Acute vasoconstriction after SAH occurs independently of changes in ICP and CPP and is associated with decreased CBF, larger hemorrhage size, persistent elevations of extracellular glutamate, and poor outcome. Acute vasoconstriction seems to contribute directly to ischemic brain injury after SAH. Further evaluations of pharmacological agents with the potential to reverse acute vasoconstriction may increase CBF and improve outcome.

Animals↗

The role of endothelium-derived nitric oxide in acetylcholine-induced coronary vasoconstriction in closed-chest pigs.

BACKGROUND: The effects of an inhibitor of endothelium-derived nitric oxide on acetylcholine (ACh)-induced coronary vasoconstriction were examined in 13 anesthetized closed-chest pigs. METHODS: Coronary blood flow was measured using a previously implanted ultrasonic transmit-time flow probe. The diameter of the large epicardial coronary arteries was assessed by coronary arteriography. RESULTS: Intracoronary infusions of ACh (0.1, 0.3, and 1.0 micrograms/kg/min) resulted in dose-dependent decreases in coronary blood flow. Arterial pressure and heart rate were minimally altered by ACh. The high dose of ACh decreased coronary blood flow by 67 +/- 11% and caused myocardial ischemia, demonstrated by ST-segment elevation. Coronary arteriograms revealed diffuse narrowing of peripheral coronary arteries and a filling delay of the contrast medium evoked with ACh. Vasospasm of the large epicardial coronary arteries was not observed. The decreases in coronary blood flow with ACh were inhibited by atropine (0.2 mg). Intracoronary administration of an inhibitor of endothelium-derived nitric oxide, NW-nitro-L-arginine (NNLA, 1.0 mg/kg), slightly increased arterial pressure but did not change baseline coronary blood flow. The percentage decreases in coronary blood flow induced by ACh were significantly augmented by NNLA administration, but those induced by prostaglandin F2 alpha (0.5 microgram/kg/min) were not affected by NNLA. The response of the large coronary arteries to ACh was not altered by NNLA. CONCLUSIONS: Our results suggest that, in pigs, ACh decreased coronary blood flow and caused myocardial ischemia as a result of the direct cholinergic vasoconstriction of peripheral small coronary arteries. The augmentation of ACh-induced coronary vasoconstriction by NNLA suggests that ACh facilitated the release of endothelium-derived nitric oxide, which attenuated the direct coronary vasoconstriction induced by ACh.

Acetylcholine↗

Platelet-activating factor is a key mediator of pulmonary vasoconstriction and bronchoconstriction after antigen challenge in the perfused sensitized rabbit lung.

Exposure of sensitized perfused rabbit lungs to human O-N type erythrocytes leads to pulmonary vasoconstriction and bronchoconstriction. To investigate whether platelet-activating factor (PAF) is a mediator of pulmonary vasoconstrictive and bronchoconstrictive responses after antigen challenge, we administered antigenic erythrocytes after the administration of PAF antagonist (.1 mg/kg; CV6209). Pulmonary arterial and airway pressures significantly increased after antigen challenge in the sensitized rabbit lungs, but not in the nonsensitized rabbit lungs. CV6209 significantly inhibited these pulmonary vasoconstrictive and bronchoconstrictive responses after antigen challenge. We concluded that PAF, at least in part, plays an important role in pulmonary vasoconstriction and bronchoconstriction after antigen challenge in rabbits.

Animals↗

Role of NO and endothelin in hemoglobin-induced pulmonary vasoconstriction.

UNLABELLED: The underlying mechanisms of hemoglobin (Hb)-induced vasoconstriction are not yet well understood. The aim of this study was to elucidate the influence of nitric oxide (NO) and endothelin (ET) on Hb-induced pulmonary vasoconstriction. Therefore, an autologous Hb preparation was administered into isolated rabbit lungs, in which pulmonary artery pressure (PAP) and weight gain was monitored. Either glyceroltrinitrate (GTN; 10(-5) M; n=6), L-arginine (10(-2) M; n=6), L-NAME (10(-4)M; n=6), ET(A)- or ET(B)-receptor antagonists (BQ,23, 10 6M, n=6) or (BQ788, 10(-6) M, n=6) were added to the perfusion fluid and NOx and thromboxane A2 levels were measured. RESULTS: In the control group the Hb-stimulation resulted in a pressure response up to 25.1+/-2.1 mmHg (p < .05), which was 136+/-6% of the reference value. The PAP increase was significantly (p < .05) blunted after GTN (71+/-5%), L-arginine (93+/-6%) and BQ788 (88+/-7%). Pretreatment with L-NAME (139+/-13%) or BQ123 (115+/-9%) did not show significant changes in PAP. CONCLUSION: The reduction of the Hb-induced pulmonary hypertension by NO-donors points toward the inactivation of NO by free hemoglobin. Likewise, ET(B)-receptor mediated vasoconstrictive effects without changes in NOx concentrations seem to play a pathogenetic role in the Hb-induced pulmonary vasoconstriction.

Animals↗

Rho-kinase inhibition blunts renal vasoconstriction induced by distinct signaling pathways in vivo.

In addition to intracellular calcium, which activates myosin light chain (MLC) kinase, MLC phosphorylation and hence contraction is importantly regulated by MLC phosphatase (MLCP). Recent evidence suggests that distinct signaling cascades of vasoactive hormones interact with the Rho/Rho kinase (ROK) pathway, affecting the activity of MLCP. The present study measured the impact of ROK inhibition on vascular F-actin distribution and on vasoconstriction induced by activation/inhibition of distinct signaling pathways in vivo in the microcirculation of the split hydronephrotic rat kidney. Local application of the ROK inhibitors Y-27632 or HA-1077 induced marked dilation of pre- and postglomerular vessels. Activation of phospholipase C with the endothelin ET B agonist IRL 1620, inhibition of soluble guanylyl cyclase with 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ), or inhibition of adenylyl cyclase with the adenosine A1 agonist N6-cyclopentyladenosine (CPA) reduced glomerular blood flow (GBF) by about 50% through vasoconstriction at different vascular levels. ROK inhibition with Y-27632 or HA-1077, but not protein kinase C inhibition with Ro 31-8220, blunted ET B-induced vasoconstriction. Furthermore, the reduction of GBF and of vascular diameters in response to ODQ or CPA were abolished by pretreatment with Y-27632. ROK inhibitors prevented constriction of preglomerular vessels and of efferent arterioles with equal effectiveness. Confocal microscopy demonstrated that Y-27632 did not change F-actin content and distribution in renal vessels. The results suggest that ROK inhibition might be considered as a potent treatment of renal vasoconstriction, because it interferes with constriction induced by distinct signaling pathways in renal vessels without affecting F-actin structure.

Adenosine↗

Acute and chronic effects of free radicals on alpha1-adrenergic-induced vasoconstriction in mesenteric beds of spontaneously hypertensive rats.

OBJECTIVE: To determine whether free radicals participate in the increased sensitivity of the alpha-adrenergic pathway in mesenteric arteries from spontaneously hypertensive rats (SHRs). METHODS AND RESULTS: SHRs are characterized by a greater vasoconstriction (P < 0.001) in response to phenylephrine in isolated and perfused mesenteric arteries. Deferoxamine (DFX) produced a significant increase in the phenylephrine-induced vasoconstriction in isolated mesenteric beds from both SHRs (P < 0.001) and Wistar-Kyoto (WKY) rats (P < 0.05), but with a greater magnitude in SHRs (P < 0.01). Acutely, activation of the hypoxanthine-xanthine oxidase (HX-XO) system produced an endothelium- and NO-dependent vasoconstriction at low concentration (P < 0.01), followed by an endothelium-independent vasorelaxation at greater concentrations in phenylephrine-preconstricted mesenteric beds (P < 0.01). Catalase and SOD (P < 0.01) prevented this endothelium-dependent response, whereas the endothelium-independent vasorelaxation induced by HX-XO was blocked by catalase, SOD and DFX (P < 0.01). Chronic administration of a diet deficient in selenium and vitamin E decreased the glutathione peroxidase activity in erythrocytes and plasma from SHRs and WKY rats (P < 0.001). Moreover, the deficient diet significantly increased the sensitivity of mesenteric arteries to phenylephrine in SHRs (P < 0.001) and WKY rats (P < 0.05), whereas it decreased acetylcholine-induced vasodilatation in SHRs only (P < 0.05). The KCl-induced vasoconstriction in response to oxygen radicals was enhanced only in mesenteric bed from SHRs. CONCLUSION: Free radicals seem to potentiate the alpha-adrenergic pathway acutely in low concentrations and to sensitize this pathway chronically in SHRs. These observations may explain the potentiated response to alpha-adrenergic agonists observed in SHRs.

Acute Disease↗

The actions of saralasin on the renal circulation of man and dog; evidence for a sympathetic neural component to vasoconstriction.

The mechanism of renal vasoconstriction produced by saralasin and its dependence on the sympathetic nervous system was investigated in subjects with mild essential hypertension and in anaesthetized dogs. Fluid or saline was given to maximize agonist vasoconstrictor responses. The changes in renal haemodynamics produced by intravenously infused saralasin (dose 0.01-10 microgram kg-1 min-1) were assessed by clearance methods. In the patients, it induced a dose-related renal vasoconstriction which correlated with a rise in plasma noradrenaline levels. In dogs with innervated kidneys it also caused vasoconstriction. But in dogs with denervated kidneys it caused vasodilatation. Infusion at the highest dose directly into the renal artery of denervated kidneys induced only vasodilatation. We conclude that one component of the renal vasoconstriction that occurs with intravenous saralasin infusions is mediated by the renal nerves.

Adult↗

Alpha-agonist modifies baroreflex vasoconstriction by a postjunctional mechanism in dogs.

1. We examined whether or not circulating alpha-agonist modified baroreflex vasoconstriction of the hindlimb, using anaesthetized dogs in which the limb was vascularly isolated and perfused with blood from a donor dog using a pulsatile pump. 2. The open-loop gain (G) of the baroreflex was estimated from changes in mean arterial pressure following mild quick haemorrhage from the aorta of the recipient dog. 3. The hindlimb perfusion pressure increased after haemorrhage due to neurogenic vasoconstriction. 4. An overall gain (Gh) of the baroreflex hindlimb vascular bed control system was estimated from the ratio of the increase in hindlimb perfusion pressure to the change in systemic arterial pressure of the recipient dog. 5. Administration of a relatively selective alpha 1-agonist with no prejunctional beta 2 stimulating action (phenylephrine) or a selective alpha 2-agonist (clonidine) to the donor dog increased its systemic arterial pressure and augmented Gh. 6. Since both drugs were administered to the donor dog and could not enter into the recipient dog, these drugs did not affect the recipient's sympathetic nervous system, including the central nervous system and afferent limb of the baroreflex system. Therefore, these drugs could modify baroreflex vasoconstriction of the hindlimb only at the junction of the efferent sympathetic nerve and the vascular smooth muscle. 7. It was concluded that postjunctional alpha-adrenoceptor stimulation augments neurogenic vasoconstriction.

Adrenergic alpha-Agonists↗