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 541 records · Page 30Linked to original sources
PubMed1995

Assessment of left ventricular myocardial perfusion and diastolic function during acetylcholine-induced diffuse coronary vasoconstriction by Doppler echocardiography and thallium-201 scintigraphy.

BACKGROUND: We investigated whether diffuse coronary vasoconstriction induced by acetylcholine caused myocardial ischemia. METHODS: We studied 30 patients (40 coronary arteries) with spontaneous chest pain or equivocal studies on treadmill exercise testing and no significant coronary stenosis or previous myocardial infarction. During the acetylcholine provocation test, Doppler echocardiography was performed, and thallium-201 was injected intravenously for scintigraphy. We used Doppler echocardiography to measure the ratio of early-to-late peak mitral flow (E:A ratio). RESULTS: When acetylcholine was injected, the coronary arteries showed three different responses. Diffuse coronary vasoconstriction without chest pain or ischemic changes on the ECG was induced in 18 (45%) arteries and the E:A ratio decreased from 0.83 +/- 0.13 to 0.77 +/- 0.13 (P = 0.031). In 17 vessels (control arteries), the E:A ratio did not change significantly (from 0.88 +/- 0.15 to 0.88 +/- 0.18; P = 0.95). In five arteries, focal spasm was induced and the E:A ratio decreased from 0.83 +/- 0.18 to 0.66 +/- 0.13 (P = 0.043). Transient defects on thallium-201 scintigraphy were observed in the territory of eight (80%) arteries with diffuse vasoconstriction and in one (20%) control artery (P = 0.047). CONCLUSIONS: Diffuse coronary vasoconstriction induced by intracoronary acetylcholine can decrease the regional myocardial blood flow (as shown by thallium-201 scintigraphy) and can cause global left ventricular diastolic dysfunction (as shown by the results of Doppler echocardiography).

Acetylcholine↗
PubMed1995

[Clinical significance of diffuse vasoconstriction of coronary arteries--a study using hyperventilation thallium-201 myocardial imaging].

Hyperventilation Thallium-201 imaging was evaluated for the examination of the existence of ischemia in the cases of diffuse vasoconstriction under the ergonovine maleate provocative test for coronary artery. Transient myocardial perfusion defect (PD) was demonstrated in 14 patients with ergonovine induced vasospasm (group S), and 13 of these patients also demonstrated redistribution (RD) (92.4%). In 14 patients with diffuse vasoconstriction (group D), nine demonstrated PD, and all of them revealed RD. On the other hand, only one of ten (10%) patients demonstrated PD and RD in a group of patients without spasm or diffuse vasoconstriction (group N). In addition, the left ventricular myocardium was divided into nine segments on a SPECT image, and the mean minimum washout rate (WOR) of each segment was evaluated. These values were compared with the percent change of the lung/heart ratio between early and delayed images (delta L/H%). Both the mean minimum WOR mean and delta L/H% of group D were significantly smaller than that of group N (p < 0.001), and only approximated to group S. Thus, the possibility of myocardial ischemia of diffuse vasoconstrictive coronary artery is implicated and such patients are supposed to be treated medically as vasospastic angina.

Aged↗
PubMedDate not supplied

Epinephrine prolongs duration of subcutaneous infiltration of local anesthesia in a dose-related manner. Correlation with magnitude of vasoconstriction.

BACKGROUND AND OBJECTIVES: Epinephrine is frequently combined with local anesthesia to prolong analgesia. Determination of the minimal concentration and the dose of epinephrine that produces prolongation of analgesia is important in the face of epinephrine's potential for systemic and local toxicity. The authors undertook this study to determine a dose-response curve of epinephrine on duration of analgesia of both 1% lidocaine and 0.25% bupivacaine after local infiltration. In order to determine whether epinephrine-induced vasoconstriction affected duration of analgesia, the authors correlated duration of analgesia with magnitude of local vasoconstriction as measured with laser Doppler flowmetry. METHODS: Six volunteers were studied in a randomized double-blind manner. Ten skin wheals of 0.2 mL solution were subcutaneously injected into both forearms of each volunteer. The solutions consisted of 1% lidocaine with epinephrine concentrations of 0, 1:50,000, 1:200,000, 1:800,000, and 1:3,200,000, and 0.25% bupivacaine with the same epinephrine concentrations. Duration of loss of sensation to pinprick at each wheal was recorded. Skin wheals with 0.2 mL of these same solutions were also subcutaneously injected into the abdomen of the same 6 volunteers, and laser Doppler flowmetry readings of skin blood flow were measured for 6 hours after injection. RESULTS: Epinephrine prolonged duration of analgesia for both lidocaine and bupivacaine in a dose-related manner (P < .001). All concentrations of epinephrine attenuated the vasodilation observed in the first 15 minutes after injection with plain local anesthesia (P = .03), and blood flow returned to baseline by 30 minutes after injection of either plain or epinephrine-containing solutions. Duration of analgesia correlated with magnitude of vasoconstriction only at the 15-minute measurement (r = .53 and .57, P = .003 and 0.001 for lidocaine and bupivacaine, respectively). CONCLUSIONS: Epinephrine prolongs duration of analgesia after local infiltration in a dose-related manner. Addition of epinephrine in concentrations of 1:50,000 or 1:200,000 increases duration of analgesia after local infiltration by approximately 200%. Addition of doses as dilute as 1:3,200,000 still increases duration of analgesia by approximately 100%. Duration of analgesia appears to correlate with magnitude of epinephrine-induced vasoconstriction using laser Doppler flowmetry. Based on study data, the use of epinephrine in concentrations from 1:200,000 to 1:3,200,000 is recommended for prolongation of analgesia after local infiltration.

Adrenergic Agonists↗
PubMedDate not supplied

K+ channel-opening action contributes to the preventive effects of nicorandil on U46619-induced vasoconstriction of canine large coronary arteries in vivo.

The antispasmogenic effects of nicorandil on epicardial coronary artery vasoconstriction were compared with those of a K+ channel opener, cromakalim, and a nitrovasodilator, nitroglycerin, in open-chest dogs. Intracoronary administration of U46619 (0.5-1.0 micrograms), a stable thromboxane A2 analogue, reduced the external diameter of the left circumflex coronary artery with no marked alternations in systemic hemodynamics. This U46619-induced vasoconstriction of large epicardial coronary arteries was dose-dependently prevented by the intracoronary infusion of nicorandil (1-10 micrograms/kg/min), cromakalim (0.03 micrograms/kg/min) and nitroglycerin (1 micrograms/kg/min). After pretreatment with glibenclamide (3 mg/kg, i.v.), and ATP-sensitive K+ channel blocker, these effects of nicorandil and cromakalim were inhibited significantly, whereas the response to nitroglycerin remained unchanged. Nicorandil (3 micrograms/kg/min), cromakalim (0.03 micrograms/kg/min) and nitroglycerin (1 micrograms/kg/min) increased coronary blood flow. However, the inhibitory effects of each drug on the U46619-induced vasoconstriction were not influenced by the partial occlusion of the left circumflex coronary artery, which kept coronary blood flow constant. This indicates a direct antispasmogenic effect of K+ channel openers, which is independent of that mediated by the response to flow. Furthermore, our results suggest that, by this effect, nicorandil protects large coronary arteries from U46619-induced vasoconstriction.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1999

Effects of candesartan on angiotensin II-induced renal vasoconstriction in rats and mice.

This study determined the inhibitory effect of the angiotensin II (AngII) type I (AT1) receptor blocker candesartan on renal vascular reactivity in vivo. Reactivity to AngII before and during candesartan administration was assessed by measuring (by electromagnetic or ultrasonic flowmetry) renal blood flow responses to AngII in rats and mice. AngII produced greater renal vasoconstriction in 7-wk-old, spontaneously hypertensive rats than in Wistar-Kyoto rats. After indomethacin treatment, AngII (2 ng) produced 40% reductions in renal blood flow in both rat strains, without affecting systemic arterial pressure. Coadministration of candesartan blocked AngII effects in a dose-dependent manner, with similar levels of inhibition in spontaneously hypertensive rats and Wistar-Kyoto rats; maximal inhibition was 80%. In rats that had been pretreated (for 30 min) with intravenous candesartan, AngII-induced renal vasoconstriction was inhibited dose dependently up to 98%. To evaluate receptor subtype mediation, responses were compared in mice with or without the AT1A receptor (deleted by gene targeting). Intrarenal AngII (1 ng) caused a 32% reduction of renal blood flow in wild-type mice and an 8% reduction of renal blood flow in AT1A receptor-knockout mice. Ten nanograms of AngII were required to elicit 20% renal vasoconstriction in these mutant mice. Concurrent injection of candesartan caused dose-dependent inhibition of AngII up to 80%. The candesartan IC50 values for percentage changes in renal blood flow did not differ in the two groups of mice. These studies establish that candesartan is an effective, highly selective, AT1 receptor blocker, inhibiting renal vasoconstriction in rodents in a concentration- and time-dependent manner. Candesartan effectively blocks AT1A and AT1B receptors in renal resistance vessels of rodents, with similar efficacies in rats and mice.

Angiotensin II↗
PubMed1977

Reduction of hypoxic pulmonary vasoconstriction by diethyl ether in the isolated perfused cat lung: the effect of acidosis and alkalosis.

Hypoxic pulmonary vasoconstriction is a protective mechanism diverting pulmonary blood flow away from hypoxic areas toward more optimally oxygenated lung units. Venous admixture is reduced and arterial oxygenation improved. Hypoxic pulmonary vasoconstriction was demonstrated during acidosis, alkalosis and normal pH in the isolated perfused cat lung under conditions of constant flow and constant left atrial and airway pressures. Two per cent diethyl ether markedly reduced hypoxic vasoconstriction under all acid-base conditions, the hypoxic pressor response returning after wash-out of diethyl ether. Modification of hypoxic pulmonary vasoconstriction during acid-base disturbances and possible implications of concurrent anaesthetic administration are discussed.

Acidosis↗
PubMed1994

Role of K+ channels in neuropeptide Y-induced vasoconstriction in rabbit cerebral basilar artery.

The role of K+ channels in the direct vasoconstrictive response induced by neuropeptide Y was investigated in isolated basilar arteries of rabbits and in vivo in rats. K+ channel openers, either BRL38227 or diazoxide, caused dose-dependent and complete relaxation of isolated arteries precontracted by neuropeptide Y. Exposure to both BRL38227 and diazoxide shifted the concentration-response curves for neuropeptide Y to the right without changing the maximal response. However, BRL38227 antagonized the angiotensin II-induced vasoconstriction noncompetitively. In vivo, the pressor responses produced by neuropeptide Y were significantly inhibited by pretreatment with BRL38227 in anesthetized rats. These results show that K+ channel openers antagonize neuropeptide Y-induced vasoconstriction in a competitive manner and suggest that blockade of K+ channels contributes, at least in part, to the direct vasoconstrictive effect of neuropeptide Y.

Animals↗
PubMed2005

Role of cytosolic phospholipase A2 in the enhancement of alpha2-adrenoceptor-mediated vasoconstriction by the thromboxane-mimetic U46619 in the porcine isolated ear artery: comparison with vasopressin-enhanced responses.

Pre-contraction with the thromboxane-mimetic U46619 enhances the subsequent alpha(2)-adrenoceptor-mediated vasoconstriction in the porcine ear artery through an enhanced activation of ERK-MAP kinase. In this study we determined the role of cPLA(2) in this enhanced response, and determined whether vasopressin is also able to enhance alpha(2)-adrenoceptor-mediated vasoconstriction through the same pathway. The cPLA(2) inhibitors AACOCF3 (50 microM) and MAFP (50 microM) both inhibited the U46619-enhanced alpha(2)-adrenoceptor response, but had no effect on the direct alpha(2)-adrenoceptor response. AACOCF3 also inhibited the enhanced ERK activation associated with the enhanced alpha(2)-adrenoceptor-mediated vasoconstriction. Pre-contraction with arachidonic acid mimicked the effect of U46619 by enhancing the contractile response to the alpha(2)-adrenoceptor agonist UK14304 (1 microM) and enhancing the alpha(2)-adrenoceptor-mediated ERK activation. Pre-contraction with vasopressin also enhanced the contractile response to UK14304, but neither PD98059 (50 microM) nor AACOCF3 (50 microM) had any effect this vasopressin-enhanced response, indicating that neither the ERK pathway, nor cPLA(2) are involved in vasopressin-enhanced responses. The alpha(2)-adrenceptor-stimulated activation of ERK was also unaffected by pre-contraction with vasopressin. On the other hand, inhibition of PKCzeta inhibited the enhanced alpha(2)-adrenoceptor contraction after pre-contraction with both U46619 and vasopressin. This study demonstrates that alpha(2)-adrenoceptor-mediated vasoconstriction can be enhanced through two different pathways-one dependent upon the enhanced activation of ERK-MAP kinase through activation of cPLA(2), and the other through a different, ERK/cPLA(2)-independent pathway.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2004

Effects of chronic PGHS-2 inhibition on PGHS-dependent vasoconstriction in the aged female rat.

OBJECTIVE: In menopause, aging and decreased estrogen levels are risk factors contributing to impaired vascular function. Previously, in a young ovariectomized rat model, we demonstrated an increase in prostaglandin H synthase (PGHS)-dependent vasoconstriction that could be prevented by estrogen replacement. Subsequently, we found that, with aging, estrogen acts through suppression of the PGHS-2 isoform. HYPOTHESIS: Chronic PGHS-2 inhibition reduces PGHS-dependent vasoconstriction in aging. METHODS: Ovariectomized, aged (12 months) Sprague-Dawley rats were treated with a placebo (n=7), or the PGHS-2 inhibitor (NS-398, s.c. 3 mg/kg) for 1 week (n=6) or 4 weeks (n=6). Methacholine (endothelium-dependent dilator) and phenylephrine (adrenergic constrictor) were used to assess vascular function in the absence or presence of the nonselective PGHS inhibitor, meclofenamate (1 micromol/l) or the specific PGHS-2 inhibitor NS-398 (10 micromol/l). RESULTS: One week of chronic PGHS-2 inhibition abolished a PGHS-dependent shift in methacholine-induced relaxation, while modulation was still observed in phenylephrine constriction. Surprisingly, 4 weeks of PGHS-2 inhibition enhanced PGHS-dependent modulation of vasoconstriction (P<0.05). PGH2/thromboxane inhibition (U-51605, 50 micromol/l) mimicked the results observed with PGHS inhibition among the groups. PGHS-2 expression increased with chronic PGHS-2 inhibition compared to control (P<0.05). CONCLUSIONS: Our data indicate a paradoxical increase in PGHS-dependent vasoconstriction and PGHS-2 expression with prolonged inhibition of PGHS-2 activity. Hence, inhibitors of PGHS-2 activity may not be beneficial in counteracting the vascular dysfunction seen with aging and menopause.

Animals↗
PubMed2000

Reversal of glibenclamide-induced coronary vasoconstriction by enhanced perfusion pulsatility: possible role for nitric oxide.

OBJECTIVES: ATP-sensitive potassium channels (K+ATP) prominently contribute to basal coronary tone; however, flow reserve during exercise remains unchanged despite channel blockade with glibenclamide (GLI). We hypothesized that increasing perfusion pulsatility, as accompanies exercise, offsets vasoconstriction from K+ATP-channel blockade, and that this effect is blunted by nitric oxide synthase (NOS) inhibition. METHODS: In 31 anaesthetized dogs the left anterior descending artery was blood-perfused by computer-controlled servo-pump, with real-time arterial perfusion pulse pressure (PP) varied from 40 and 100 mm Hg at a constant mean pressure and cardiac workload. RESULTS: At control PP (40 mm Hg), GLI (50 micrograms/min/kg, i.c.) lowered mean regional coronary flow from 37 +/- 5 to 25 +/- 4 ml/min (P < 0.001). However, this was not observed at 100 mm Hg PP (41 +/- 2 vs. 45 +/- 4). NOS inhibition by NG-monomethyl-L-arginine (L-NMMA) did not alter basal flow at 40 mm Hg PP, but modestly lowered flow (-5%, P < 0.001) at higher PP (100 mm Hg), reducing PP-flow augmentation by -36%, and acetylcholine (ACh) induced flow elevation by -39%. Co-infusion of L-NMMA with GLI resulted in net vasoconstriction at both PP levels (-60% and -40% at 40 and 100 mm Hg PP, respectively). Unlike GLI, vasoconstriction by vasopressin (-43 +/- 3% flow reduction at 40 mm Hg PP) or quinacrine (-23 +/- 7%) was not offset at higher pulsatility (-44 +/- 4 and -23 +/- 6%, respectively). Neither of the latter agents inhibited ACh- or PP-induced flow responses, nor did they modify the effect of L-NMMA on these responses. CONCLUSIONS: Increased coronary flow pulsatility offsets vasoconstriction from K+ATP blockade by likely enhancing NO release. This mechanism may assist exercise-mediated dilation in settings where K+ATP opening is partially compromised.

Acetylcholine↗
PubMed1998

Neuropeptide Y-induced potentiation of noradrenergic vasoconstriction in the human saphenous vein: involvement of endothelium generated thromboxane.

1. We investigated the potentiating effect of low concentrations of neuropeptide Y (NPY) on the vasoconstriction induced by transmural nerve stimulation (TNS) and noradrenaline (NA) in human saphenous veins. The effects of (i) endothelium removal; (ii) the addition of the NO pathway precursor L-arginine; (iii) the ET(A)/ET(B) endothelin receptor antagonist Ro 47-0203; (iv) the cyclo-oxygenase inhibitor, indomethacin; (v) the selective thromboxane A2 (TxA2) receptor antagonists Bay u3405 and ifetroban, and (vi) the TxA2 synthase inhibitor, UK 38485, were studied in order to gain information about the mechanisms of NPY-induced potentiation. 2. Contractile response curves for TNS (0.5-8 Hz) and for exogenously administered NA (0.1-3 microM) were obtained in superfused saphenous vein rings. The contractions induced by both TNS and NA at all tested frequencies and concentrations, respectively, were significantly potentiated by 50 nM NPY in endothelium intact veins. Conversely, in endothelium-denuded vessel rings the contractile-response curves to TNS and NA overlapped both in the absence and presence of NPY, thus suggesting that a release of vasoactive substances from endothelial cells could account for the noradrenergic NPY-induced potentiation. 3. In vessels with intact endothelium, the potentiating action of NPY on TNS and NA was unaffected by the presence of high concentrations of the NO precursor L-arginine (3-10 mM) or the non-selective ET(A)/ET(B) endothelin receptor antagonist, Ro 47-0203 (10 microM). These data indicate that the NPY-induced effect does not involve either the endothelium-derived vasodilator nitric oxide or the vasoconstrictor endothelin. Conversely, in the presence of the cyclo-oxygenase inhibitor, indomethacin (30 microM), NPY failed to potentiate the vasoconstrictions produced by either nerve stimulation or by exogenous NA, thus providing evidence that arachidonic acid metabolites through the cyclo-oxygenase pathway are mainly responsible for the potentiation evoked by NPY. 4. When the TxA2 receptor antagonists, Bay u 3405 (1 microM) and ifetroban (1 microM) were added to the superfusing medium, NPY did not alter either the frequency- or the concentration-response curves for either TNS or NA. Accordingly, both TNS- and NA-induced contractions were not potentiated by NPY in the presence of the TxA2 synthase inhibitor, UK 38485 (10 microM). This clearly demonstrates the pivotal role of TxA2 in NPY-induced potentiation. 5. In superfused vein rings with endothelium, a subthreshold concentration (0.2 nM) of the TxA2 mimetic U 46619 potentiated both TNS- and NA-induced vasoconstrictions. This potentiation was higher at low stimulation frequencies and low NA concentrations, and resembled that produced by NPY. 6. Our results indicate that in the human saphenous vein NPY potentiates the contractions produced by sympathetic nerve stimulation acting at the postjunctional level, primarily on endothelial cells. In particular, the NPY-induced release of a cyclo-oxygenase metabolite, namely TxA2, may have a synergistic effect on the vasoconstriction induced by the noradrenergic mediator. Thus, such a mechanism may play a key role in the maintenance of the sympathetic tone of large human capacitance vessels.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2002

Forearm vasoconstriction to endothelin-1 is impaired, but constriction to sarafotoxin 6c and vasodilatation to BQ-123 unaltered, in patients with essential hypertension.

The importance of endothelin-1 (ET-1) in the pathophysiology of essential hypertension is unclear. We therefore compared the effects of endothelin ET(A) receptor blockade and the stimulation of ET(A) and ET(B) receptors, and their interaction with the sympathetic nervous system, in the forearm resistance vessels of patients with essential hypertension and healthy control subjects. A total of 27 untreated patients with essential hypertension (blood pressure >160/100 mmHg) and 25 normotensive (blood pressure <140/90 mmHg) age- and sex-matched control subjects participated in these studies. A total of 10 patients and 10 controls took part in each phase. Locally active doses of study drugs were infused into the non-dominant brachial artery, while forearm blood flow was measured by venous occlusion plethysmography. A 60 min infusion of BQ-123 (an ET(A) receptor antagonist; 100 nmol/min) significantly increased forearm blood flow by 40+/-8% in hypertensive patients and by 35+/-5% in controls, with no difference between groups (P=0.49). Forearm vasoconstriction to ET-1 (an ET(A) and ET(B) receptor agonist; 5 pmol/min) for 90 min was significantly blunted in hypertensive patients (21+/-4%) compared with control subjects (37+/-3%; P=0.0001). Forearm vasoconstriction to sarafotoxin S6c (an ET(B) receptor agonist; 10 pmol/min) for 90 min was similar in hypertensive patients (44+/-5%) and control subjects (48+/-4%; P=0.95). Sympathetically mediated vasoconstriction produced by lower-body negative pressure was not different in hypertensive patients compared with controls, and was not affected by infusion of ET-1 or sarafotoxin S6c. There were no differences in the observed increase in forearm blood flow with a control vasodilator (sodium nitroprusside) or the observed decrease in forearm blood flow with a control vasoconstrictor (noradrenaline) between hypertensive patients and control subjects. BQ-123 produced a significant increase in forearm blood flow in hypertensive patients, consistent with the anti-hypertensive actions of this agent. In conclusion, forearm vasoconstriction to ET-1, but not to sarafotoxin S6c, was reduced in patients with essential hypertension, consistent with possible down-regulation of the ET(A) receptor in this condition.

Acetylcholine↗
PubMed2003

Reversible segmental cerebral vasoconstriction (Call-Fleming syndrome): are calcium channel inhibitors a potential treatment option?

The Call-Fleming syndrome is characterized by sudden onset of thunderclap-like headache and focal neurological deficits. The pathophysiological correlate is a reversible segmental cerebral vasoconstriction frequently associated with focal cerebral ischaemia. The syndrome has been described in a variety of clinical conditions, and recently an association between the syndrome and exposure to vasoactive drugs was observed. Effective treatment options are not known. A 63-year-old female developed sudden 'worst ever' headache. Initial neurological examination, laboratory blood tests, CSF examination and brain magnetic resonance imaging (MRI) were normal. Previous medical history was unremarkable and she did not take vasoactive drugs. Eleven days after the onset of headache she developed visual field impairment and a right-sided hemiparesis. Brain MRI revealed bilateral posterior and left parietal ischaemic strokes. Cerebral catheter angiography showed segmental arterial vasoconstriction. A vasodilative therapy with calcium channel inhibitors was started and serial transcranial Doppler ultrasonography demonstrated resolution of cerebral arterial vasoconstriction. The present case illustrates that calcium channel inhibitors may be an effective therapy for segmental cerebral arterial vasoconstriction. However, more clinical data are needed to prove this observation.

Calcium Channel Blockers↗
PubMed2004

Vasopressin-induced vasoconstriction is dependent on MAPKerk1/2 phosphorylation.

To investigate the involvement of the mitogen-activated protein kinase (MAPK) family of extracellular signal-regulated kinase (ERK) 1 and 2 (MAPKerk1/2) in the vasopressin-mediated vasoconstriction in the rat aorta. Vasopressin-induced vasoconstriction was measured in isolated rat thoracic aortae in the presence or absence of MAPKerk1/2 kinase (MKKmek1/2) inhibitors. Thereafter the MAPKerk1/2 phosphorylation in the rat aorta was quantified using Western blot analysis. Vasopressin (1-300 nm) induced a concentration-dependent vasoconstriction, which could be inhibited concentration dependently by the selective MKKmek1/2 inhibitors, PD 98059 (10 and 100 microm) and U 0126 (10 and 100 microm). Western blot analysis revealed a 2.7 +/- 0.6-fold increase in the MAPKerk1/2 phosphorylation induced by vasopressin (300 nm). This phosphorylation could be dose dependently prevented by both PD 98059 (100 microm) and U 0126 (10 and 100 microm). These results indicate that vasoconstriction induced by vasopressin is partly regulated by the MAPKerk1/2 pathway.

Animals↗
PubMed1993

Action of carbon dioxide on hypoxic pulmonary vasoconstriction in the rat lung: evidence against specific endothelium-derived relaxing factor-mediated vasodilation.

OBJECTIVES: The effect of hypercapnia on pulmonary vascular tone is controversial with evidence for both a vasoconstrictor and vasodilator action. The objective of this study was to investigate the possibility that this dual response to CO2 could be explained by a direct constrictor action on smooth muscle and an indirect dilator action via the release of endothelium-derived relaxing factor. The effect of ventilation with hypercapnia (FICO2 0.15) on pulmonary pressor response to hypoxia (FIO2 0.3) was investigated. DESIGN: Prospective, randomized study. SETTING: The National Heart and Lung Institute, UK. SUBJECTS: The isolated, blood-perfused rat lung. INTERVENTIONS: Angiotensin-II and a blocker of endothelium-derived relaxing factor synthesis, NG-monomethyl-L-arginine (L-NMMA). MEASUREMENTS AND MAIN RESULTS: The vasomotor effect of hypercapnia depended on pulmonary arterial pressure. Under resting tone, CO2 acted as a mild constrictor (change in mean pulmonary arterial pressure from 14 +/- 2 to 15 +/- 2 mm Hg, n = 4; p < .05. At increased tone, induced either by hypoxia or Angiotensin-II, CO2 was a vasodilator. Thus, hypoxia increased mean pulmonary arterial pressure from 17 +/- 2 to 32 +/- 2 mm Hg (n = 8; p < .01), but simultaneous ventilation with hypoxia and hypercapnia reduced this by 16 +/- 1% (p < .01). Angiotensin-II (1 microgram) increased pulmonary arterial pressure from 14 +/- 2 to 39 +/- 5 mm Hg (n = 8; p < .01), but with hypercapnia, this angiotensin-induced pulmonary vasoconstriction was reduced by 18 +/- 6% (p < .001). The reduction in hypoxic pulmonary vasoconstriction induced by hypercapnia was not significantly different from that seen with Angiotensin-II hypercapnia. Blocking endothelium-derived relaxing factor synthesis using 30 microM NG-monomethyl-L-arginine did not significantly change either basal pulmonary arterial pressure or the response to hypercapnia, but increased hypoxic pulmonary vasoconstrictor by 24 +/- 4% (n = 4; p < .01). There was no significant difference between the change in hypoxic pulmonary vasoconstriction induced by hypercapnia after saline control (21 +/- 8% decrease) and the change in hypoxic pulmonary vasoconstriction caused by CO2 after 30 microM L-NMMA (25 +/- 10% decrease, p < .05, n = 8). CONCLUSION: Endothelium-derived relaxing factor seems unlikely to specifically modulate CO2-induced vasodilation in the rat pulmonary circulation.

Angiotensin II↗
PubMed1967

Pulmonary vasoconstriction in asphyxia during cross-circulation between twin foetal lambs.

1. The effect of asphyxia on pulmonary vascular resistance was measured in anaesthetized foetal lambs whose left lung was supplied with arterial blood from a twin, both still being attached to their placentas by intact umbilical cords.2. In foetal lambs of 91-92 days gestation asphyxia of the recipient caused no pulmonary vasoconstriction so long as its left pulmonary artery was supplied with normal blood from a twin donor. Asphyxia of the donor caused pulmonary vasoconstriction in the unasphyxiated recipient; this was therefore wholly due to a local effect of the blood passing through the lung.3. In foetal lambs of 98-142 days gestation asphyxia of the recipient caused a small degree of pulmonary vasoconstriction, even though the left pulmonary artery was supplied with normal blood from the twin donor. This vasoconstriction was abolished by administration of hexamethonium or by cutting the sympathetic nerves to the left lung.4. In mature foetal lambs pulmonary arterial inflow and venous outflow were measured simultaneously. Broncho-pulmonary blood flow was less than 5% of total pulmonary flow. Pulmonary O(2) consumption was 0.75 +/- 0.11 ml./100 g.min, or about 5% of total foetal O(2) consumption.

Animals↗
PubMed1996

Role of protein kinase C in angiotensin II-induced renal vasoconstriction in genetically hypertensive rats.

The renal vasculature of young spontaneously hypertensive rats (SHR) responds to angiotensin II (ANG II) with exaggerated vasoconstriction, due in part to defective buffering by the adenosine 3',5'-cyclic monophosphate (cAMP) pathway. In vitro studies suggest greater activation of phospholipase C and protein kinase C (PKC) in cultured mesangial cells and vascular smooth muscle cells. The present studies evaluated the role of PKC activation in renal vascular responses to ANG II receptor activation and the relative contributions in SHR vs. Wistar-Kyoto control rats (WKY). Renal blood flow was measured in 8-wk-old anesthetized SHR and WKY pretreated with indomethacin. ANG II (2 ng) injection into the renal artery produced a transient 45-50% maximum reduction of renal blood flow in both rat strains. Intrarenal infusion of either staurosporine or chelerythrine into the renal artery effectively attenuated the vasoconstriction elicited by ANG II in a dose-dependent manner, with maximum inhibition of 60-70%. The PKC inhibitory effects were significant and independent of strain. Coadministration of the PKC inhibitors produced maximal inhibition similar to that observed with one agent, suggesting action via a common pathway. In other studies, the linkage of the PKC pathway to the AT1 receptor was evaluated using sub and maximal doses of losartan to antagonize 50-80% of ANG II-induced vasoconstriction. The same degree of inhibition was observed when a PKC inhibitor was coadministered with losartan. These findings support the views that the PKC system is a major intracellular signaling pathway coupled to the AT1 receptor in renal resistance vessels and that PKC activation is involved to similar degrees in the renal vasoconstriction elicited by ANG II in young WKY and SHR. Exaggerated vascular reactivity to vasoconstrictor agents in genetically hypertensive animals is probably due to a defect in cAMP generation in the presence of a normally operating PKC pathway.

Alkaloids↗
PubMed1976

Effect of angiotensin on hypoxic pulmonary vasoconstriction in isolated dog lung.

The effects of infused angiotensin on hypoxic pulmonary vasoconstriction in blood-perfused isolated dog lungs were studied. By using a double-perfusion system we were able to perfuse the right and left lungs separately in the same animal; one lung was used as control and the other lung was experimentally modified. The vasoconstrictive response to hypoxia decreased with time in the isolated lung preparations. The infusion of either angiotensin I or angiotensin II (1.2-5.8 mug/min) caused a threefold increase in the vasoconstrictive response to hypoxia over control levels. A second hypoxic period during the infusion usually yielded a diminished response, suggesting further degeneration of the response irreversible with angiotensin. It was concluded that angiotensin I or angiotensin II temporarily enhances hypoxic pulmonary vasoconstriction in isolated dog lungs.

Angiotensin II↗