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Reactive hyperemia unmasks reduced compliance of cutaneous arteries in essential hypertension.

To evaluate changes in distal cutaneous arteries during hypertension, we used a noninvasive method to assess the compliance and vascular resistance of the hand radial arteries, mainly distributed to the skin, in 10 normotensive and 10 hypertensive (HT) men. Radial artery diameter and blood velocity were measured by means of pulsed Doppler concomitantly with measurements of finger arterial pressure by photoplethysmography. Hand radial vascular resistance was calculated as the ratio of mean arterial pressure to mean radial blood flow. A simple resistive-capacitive model of large and small arteries of the hand allowed us to evaluate arterial compliance from the exponential slope of finger diastolic pressure decay and vascular resistance. Measurements were made at baseline and during reactive hyperemia after 5 min of complete occlusion of the brachial artery with a pneumatic cuff. Except for pressure, there were no baseline differences between the groups. In normotensive and HT subjects, hyperemia increased radial artery diameter and blood velocity (P < 0.001) and compliance (P < 0.01 and P < 0.05, respectively) and decreased mean pressure (P < 0.01 and P < 0.001, respectively) and resistance (P < 0.001). During hyperemia, the only difference between the groups, except for pressure, was lower compliance in HT subjects (P < 0.01). Moreover, compliance during hyperemia negatively correlated with baseline mean pressure (P = 0.001). Thus hyperemia unmasked reduced compliance in the HT patients but did not show abnormal resistance, suggesting that the elastic properties of the hand skin radial arteries might be more sensitive than their resistive properties to high blood pressure.

Adult↗

Unloading effects of molsidomine on peripheral circulation and cardiac hemodynamics in patients with acute myocardial infarction.

The unloading mechanisms and side of peripheral action of the new antianginal drug molsidomine was compared with isosorbide dinitrate (ISDN) in 14 patients with acute myocardial infarction using a Swan-Ganz catheter and venous occlusion plethysmography. Sublingual molsidomine (2-4 mg) increased calf venous capacitance (CVC) (0.42 +/- 0.18 to 0.64 +/- 0.09 ml/100 ml, p less than 0.05) from 30 to 240 minutes, while simultaneously lowering of PCWP (25.9 +/- 4.9 to 15.8 +/- 7.3 mmHg, p less than 0.05) and CVP (9.3 +/- 3.7 to 5.8 +/- 3.5 cmH2O, p less than 0.05). Calf blood flow (CBF), calf vascular resistance (CVR), CI, TSPR and SWI were not affected significantly. Molsidomine reduced preload more than 240 minutes after its administration. Sublingual ISDN increased CBF into the initial 15 minutes (1.19 +/- 0.49 to 1.83 +/- 0.98 ml/100ml/min, p less than 0.05) and CVC from 5 to 60 minutes (0.42 +/- 0.19 to 0.68 +/- 0.24 ml/100ml p less than 0.01) while simultaneously lowering PCWP (24.3 +/- 2.2 to 14.6 +/- 4.5 mmHg, p less than 0.01) and CVP (9.0 +/- 2.8 to 5.5 +/- 3.5 cmH2O, p less than 0.05). Neither drug affected cardiac index, blood pressure or systemic vascular resistance. These data suggest that molsidomine significantly lowered elevated preload (PCWP/PCP) by dilating venous capacitance vessels. Its length of action was 240 minutes compared with 60 minutes obtained with ISDN, which suggests this new agent may be of marked benefit in the AMI patients suffering from backward failure uncomplicated by forward failure in whom continued preload reduction is necessary. (Results are expressed as the mean +/- standard deviation).

Adult↗

Coronary arterial inflow impediment during systole is little affected by capacitive effects.

During cardiac contraction coronary arterial inflow is impeded, whereas venous flow is augmented. These effects are assumed to be caused by diameter reductions of intramyocardial blood vessels. The reduction in vascular diameter (and thus vascular volume) during contraction increases coronary resistance and/or decreases back pressure so that flow decreases and the rate of change of volume results in a capacitive flow. The aim of this study was to estimate the contribution of capacitive flow to total coronary inflow impediment. Isolated blood-perfused (100 mmHg and constant), maximally vasodilated, ryanodine-pretreated rat hearts (n = 8) with intraventricular balloons were used. The coronary inflow impediment during isovolumic beats at a heart rate of 2-3 Hz (dynamic contractions) and during prolonged systoles obtained by fast pacing (static contractions, no capacitive flow impediment) were compared. Changing left ventricular balloon volume enabled us to vary left ventricular pressure and to relate systolic flow to systolic left ventricular pressure. We found that for the same contractility (expressed in terms of systolic pressure-volume relationship and maximal elastance) and same left ventricular pressure, the ratio of coronary inflow impediment in dynamic and static contractions is not significantly different from unity (P < 0.005). This implies that under our experimental conditions coronary inflow impediment in dynamic contractions is little affected by capacitive effects.

Animals↗

Histamine selectively interrupts VE-cadherin adhesion independently of capacitive calcium entry.

Histamine is an important agent of innate immunity, transiently increasing the flux of immune-competent molecules from the vascular space to the tissues and then allowing rapid restoration of the integrity of the endothelial barrier. In previous work we found that histamine alters the endothelial barrier by disrupting cell-cell adhesion and identified VE-cadherin as an essential participant in this process. The previous work did not determine whether histamine directly interrupted VE-cadherin adhesion, whether the effects of histamine were selective for cadherin adhesion, or whether capacitive calcium flux across the cell membrane was necessary for the effects of histamine on cell-cell adhesion. In the current work we found that histamine directly interrupts adhesion of L cells expressing the type 1 histamine (H1) receptor and VE-cadherin to a VE-cadherin-Fc fusion protein. In contrast, integrin-mediated adhesion to fibronectin of the same L cells expressing the H1 receptor was not affected by histamine, demonstrating that the effects of histamine are selective for cadherin adhesion. Some of the effects of many edemagenic agonists on endothelium are dependent on the capacitive flux of calcium across the endothelial cell membrane. Blocking capacitive calcium flux with LaCl3 did not prevent histamine from interrupting VE-cadherin adhesion of transfected L cells, nor did it prevent histamine from interrupting cell-cell adhesion of human umbilical vein endothelial cells. These data support the contentions that histamine directly and selectively interrupts cadherin adhesion and this effect on cadherin adhesion is independent of capacitive calcium flux.

Animals↗

[Resistance and capacitance functions of gastric vessels under the action of noradrenaline].

In acute experiments on cats, the gastric vascular bed being perfused under constant blood flow, the actions of gastric vessels was investigated using newly elaborated approach to their humoral isolation. Increased doses of noradrenaline elicited the dose-dependent constrictive response of gastric arterial vessels. Perfusion pressure increase in the gastric vascular bed under action of the minimal dose of noradrenaline was more pronounced, than in the intestinal vessels. The capacity of the gastric vascular bed under action of the drug changed in different manner, mostly increased, but could be decreased as well. In contrast to the small intestine the gastric vessels are characterized by more pronounced action of noradrenaline on blood depoting processes.

Animals↗

Methylene blue attenuates vasodilation and enhances vasoconstriction in response to endothelin-1 in the pig nasal mucosa.

In thiopentone anaesthetized pigs (n = 10), simultaneous recordings of the vasomotor response to local intra-arterial infusion of endothelin-1 and -3 were performed in three different vascular compartments of the nasal mucosa. Sphenopalatine artery blood flow (reflecting nasal blood flow), nasal cavity volume (representing blood content in capacitance vessels) and laser Doppler flowmeter signal (reflecting superficial mucosal blood flow) increased in response to low doses (4 x 10(-9) to 4 x 10(-8) moles) of endothelin-1. In contrast, marked vasoconstriction (up to 50% of arterial blood flow reduction) occurred upon higher doses (4 x 10(-7) to 4 x 10(-6) moles). Endothelin-3 (4 x 10(-9) to 4 x 10(-6) moles) evoked at the highest dose a long-lasting increase of systemic arterial blood pressure resulting in a 22 +/- 4% increase in nasal vascular resistance. After local intra-arterial pretreatment with methylene blue (4 x 10(-4) mol), the vasodilatory responses to low doses of endothelin-1 were abolished for the three vascular parameters studied, whereas the vasoconstrictor responses in resistance and capacitance vessels evoked by higher doses of endothelin-1 were increased. In contrast, the laser Doppler flowmeter signal reduction in response to endothelin-1 was markedly attenuated. The vasodilatatory effect of substance P was abolished after methylene blue probably due to interference with effects of endothelium dependent relaxing factor (EDRF). These observations suggest that in the pig nasal mucosa in vivo, exogenous endothelin-1 induces a dose-dependent reduction of blood flow in resistance and capacitance vessels and in superficial mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Discrepancy between initial and steady-state resistance vessel responsiveness to short-term nitroglycerin exposure in the hindlimb of conscious dogs.

Since much of the antianginal efficacy of nitroglycerin can be ascribed to its ability to dilate large arteries and venous capacitance vessels at dosages that have little steady-state effect on vascular resistance, we re-examined the reasons for low responsiveness of resistance vessels to nitroglycerin in a peripheral vascular bed in vivo. In chronically instrumented conscious dogs, intra-iliac nitroglycerin (0.15, 0.5, and 1.5 micrograms/kg/min) resulted in substantial dose-dependent initial increases in iliac flow (35% +/- 7%, 60% +/- 11%, and 106% +/- 12%, respectively). However, unlike the responses of iliac large artery diameter, these dilations were not sustained during a 6-min infusion. In contrast, doses of nitroprusside, acetylcholine, and adenosine, which gave initial dilations comparable to nitroglycerin, resulted in considerably greater steady-state responses (p less than 0.001). Nitrate tolerance, autoregulatory escape, reflex vasoconstriction, and the influence of cyclooxygenase products were ruled out as potential explanations of this selective pattern of nitroglycerin response. It is proposed that the rapid attenuation of nitroglycerin-induced dilation in a representative peripheral vascular bed cannot be attributed to currently accepted hypotheses and contributes more to the unique and beneficial spectrum of nitrate vascular action than an a priori lack of sensitivity of resistance vessels.

Acetylcysteine↗

Hypotensive and vasodilator actions of SK&F 24260, a new dihydropyridine derivative.

1 The blood pressure of conscious normotensive, Goldblatt-hypertensive and genetic-hypertensive rats and normotensive dogs was lowered by SK&F 24260 (1,4-dihydro-2,6-dimethyl-4-(2-trifluormethylphenyl)-3,5-pyridinedicarboxylic acid diethyl ester).2 Tachycardia always accompanied the hypotension. In rats propranolol abolished the tachycardia but in dogs there was only a small reduction in the heart rate response.3 In conscious dogs there was an increase in left ventricular output and a marked fall in total peripheral resistance.4 SK&F 24260 dilated resistance vessels in rat hindquarters. Dilatation was caused by doses of SK&F 24260 some 50 times smaller than those of hydrallazine.5 In preparations of cat skeletal muscle and intestinal vascular beds SK&F 24260 selectively dilated resistance vessels in preference to capacitance vessels and resembled hydrallazine rather than papaverine which has no such selectivity.6 Pre-capillary sphincter vessels were also dilated by SK&F 24260. Changes in fluid equilibrium caused by SK&F 24260 were consistent with selective dilatation of resistance vessels.

Animals↗

Role of substance P in the vascular response of nasal mucosa in nasal allergy.

The effects of topically administered substance P (SP) on nasal blood flow and nasal airway resistance (NAR) were evaluated in 11 subjects with perennial nasal allergy. The change in NAR induced by SP was compared with those induced by nasal challenge with histamine, leukotriene D4 (LTD4), and antigen. In doses > or = 16 nmol, SP caused a significant increase of nasal blood flow within 5 minutes that lasted for less than 20 minutes. In doses > or = 16 nmol, SP caused a dose-dependent, short-lasting, significant increase in NAR. The magnitude of the increase in NAR was LTD4 > SP > histamine when compared on a molar basis. Our results may suggest that SP released from C fiber terminals is partially involved in an early nasal vascular response after antigen challenge by acting on adjacent vascular smooth muscle to cause a transient vasodilatation of both resistance and capacitance vessels only while sensory stimulation persists in subjects with nasal allergy.

Adolescent↗

Contracted plasma volume syndromes.

There is a wide range of disorders in which plasma volume may be contracted. This may either be due to a primary reduction in plasma volume, or secondary to a reduction in the volume of the vascular compartment. In the former there may be a salt and water deficit as the cause or a loss of plasma volume due to a capillary leak. Reduction of the vascular compartment is usually due to increased adrenergic activity reducing the circulatory capacitance volume. Plasma volume is reduced to compensate for the overfilling of the central circulation. The causes and clinical significance of plasma volume contraction are discussed, with particular emphasis on the pathophysiology and implications for therapy. The controversial subject of stress polycythaemia is addressed and a theoretical analysis of its pathophysiology presented.

Erythrocyte Indices↗

Pharmacotherapeutic stature of doxazosin and its role in coronary risk reduction.

In hypertension the primary pathophysiologic abnormality is a generalized increase in the peripheral vascular resistance as a result of concentric narrowing of the systemic arterioles, as a result of alpha 1-receptor stimulation. Such stimulation is attenuated by the selective alpha 1-inhibitor doxazosin. The pharmacologic attributes of doxazosin are translated into direct relaxation of the peripheral arteriolar resistance vessels and venous capacitance system, particularly those with a high alpha-adrenoceptor population. The direct effects of such vascular dilatation are immediately beneficial to the heart in reducing systemic and pulmonary vascular pressures that reduce left ventricular wall stress and myocardial oxygen consumption. In clinical studies doxazosin has been found to have a plasma half-life of 19 to 22 hours, of which a single daily dose is sufficient to control hypertension. The antiatherogenic changes in the blood lipid profile resulting from long-term treatment with doxazosin can also be expected to advance its primary prevention potential in hypertensive patients, which is in marked contrast to the potentially disadvantageous changes in the blood lipid profile that follow treatment with beta-blockers and thiazide diuretics. The therapeutic efficacy of doxazosin has been confirmed, irrespective of hypertension severity, age and race of the patient, or the presence of renal impairment or diabetes mellitus. Its side-effect profile is not substantially different from that of placebo or other antihypertensive drug treatment. Given its unique actions regarding antihypertensive efficacy, together with favorable effects on blood lipids, doxazosin probably holds more promise for the prevention of precocious coronary heart disease in hypertensive patients than any other currently available antihypertensive agent.

Adrenergic alpha-Antagonists↗

Active and passive liver microvascular responses from angiotensin, endothelin, norepinephrine, and vasopressin.

Vasoconstrictor agents may induce a decrease in hepatic vascular volume passively, by decreasing distending pressure, or actively, by stimulating contractile elements of capacitance vessels. Hepatic venular resistance was estimated in anesthetized rabbits from hepatic venular pressure (P(mu hv); by servo-null micropipette), inferior vena cava pressure, and total hepatic blood flow (F(hv); by ultrasound flow probe). Changes in liver volume were estimated from measures of liver lobe thickness. Angiotensin (ANG) II, endothelin (ET)-1, norepinephrine (NE), and vasopressin (VP) were infused into the portal vein at a constant rate for 5 min. We conclude that ANG II and NE induced active constriction of hepatic capacitance vessels, because the liver lobe thickness decreased significantly even though P(mu hv) and portal venous distending pressure (P(pv)) increased. All four agents increased splanchnic and hepatic venous resistances in similar proportions. With VP, P(mu hv) and P(pv) decreased, but with ET-1, P(mu hv) and P(pv) increased. However, lobe thickness was not significantly changed by either drug during the infusion compared with the 2-min control period. Thus VP and ET-1 have only minor effects on hepatic capacitance vessels. ET-1, at 0.04 microg. min(-1). kg body wt(-1), caused an increase in systemic arterial blood pressure, but erythrocyte movement through the sinusoids in some animals stopped.

Angiotensin II↗

Cardiovascular effects of a novel enkephalin analogue, 443C81, in humans.

The cardiovascular effects of a novel enkephalin analogue, 443C81 (Tyr-D-Arg-Gly-Phe(4NO2)-Pro.NH2), were studied in healthy volunteers. According to a double-blind, cross-over, randomised, balanced design, six men received two different doses of 443C81 or saline as intravenous (i.v.) infusions on three occasions. Mean +/- SD plasma concentrations achieved at steady state were 0.46 +/- 0.11 microgram/ml after low-dose 443C81 and 1.0 +/- 0.2 microgram/ml after high-dose 443C81. In the supine position, low and high doses produced mean transient increases in diastolic blood pressure (DBP) of 5 and 4 mm Hg and heart rate (HR) of 5 and 12 beats/min, respectively. With the higher dose, these changes were followed by a mean decrease in DBP of 8 mm Hg while HR returned to control values. When the subjects were tilted, the pressor effect was not observed, and hypotension occurred earlier and was more pronounced. Both doses reduced forearm and systemic vascular resistance, and there was a dose-related increase in supine forearm venous capacitance; venoconstriction associated with tilting was unaffected by 443C81. Plasma renin activity and elevation of epinephrine concentrations on tilting were increased by the enkephalin, which also caused a diuresis through an increase in free water clearance.

Adult↗

Effect of adrenergic neuron inhibitors on the vascular response to sympathetic nerve stimulation.

In anesthetized cats, the lumbar sympathetic trunk was stimulated, and the responses of the resistance and capacitance vessels of the hindlimb were recorded (by resistography and plethysmography, respectively). The drugs used were reserpine, methyldopa and bretylium tosylate. It was found that reserpine and methyldopa inhibit the response of the resistance vessels to a greater extent than that of the capacitance vessels, while bretylium tosylate has a greater effect on the transmission of constrictor impulses to the capacitance vessels. Reserpine mainly suppresses responses to low-frequency stimulation and bretylium tosylate--those to high-frequency stimulation, while methyldopa affects them to the same degree at all frequencies.

Animals↗

Large pulmonary arteries and the control of pulmonary vascular resistance in the newborn.

In the immediate neonatal period the pulmonary vascular resistance is higher than later in life. The role of maturational differences in the smooth muscle mechanical properties of large capacitance vessels in this response has not been previously studied. To this end, we studied the smooth muscle isometric and isotonic mechanical properties, as well as the myogenic response of large extralobar pulmonary arteries in newborn and adult guinea pigs. Compared with the adult, the newborn pulmonary vascular smooth muscle generates less force and has a similar shortening capacity but longer isometric and isotonic relaxation half times. The myogenic response could be elicited in 80% of the newborn and 70% of the adult vessels. A 20% increase in vessel diameter resulted in force generation equivalent to 46 +/- 5.1% of maximal isometric tension in the newborn. Such a response was significantly greater than observed for the adult vessels (14 +/- 2.8%; p < 0.001). Our results showed significant maturational differences in the mechanical properties of the large pulmonary artery smooth muscle in the newborn. We speculate that the presence of myogenic response in large pulmonary capacitance vessels and the observed greater magnitude of stretch-induced force generation in the newborn may play an important role in the maintenance of a higher pulmonary vascular resistance in the neonatal period.

Aging↗

Comparison between pial and intraparenchymal vascular responses to cervical sympathetic stimulation in cats. Part 1. Under normal resting conditions.

To investigate the role of sympathetic regulation in both resistance and capacitance vessels in cerebral circulation, the response of pial and intraparenchymal vessels to sympathetic nerve stimulation were simultaneously examined in 14 cats by means of a newly developed video camera photoelectric system. The system consisted of a video camera system for measurement of pial vascular diameters and a photoelectric apparatus for estimating regional cerebral blood volume in the intraparenchymal vessels. The ipsilateral superior cervical ganglion was electrically stimulated for 5 min. Initially, both the pial and intraparenchymal vessels constricted. The large pial arteries (173 +/- 25 micron, mean +/- SEM) remained constricted throughout the stimulation, whereas the intraparenchymal vessels began to dilate after the initial constriction and exceeded the control level at 175 +/- 25 s despite continued stimulation. In conclusion, such sympathetic nerve stimulation is considered to exert a constrictive effect on the intraparenchymal as well as the pial vessels at the early stage. The compensatory dilation of the intraparenchymal vessels was delayed 3 min after initiation of the stimulation.

Animals↗

Measurements of vascular function using strain-gauge plethysmography: technical considerations, standardization, and physiological findings.

The main purpose of the present study was to examine the relationships between measures of fitness [estimated peak oxygen consumption (V(O2) peak) and handgrip strength] and forearm vascular function in 55 young (22.6 +/- 3.5 yr) adults. In addition, the present study considered methodological and technical aspects regarding the examination of the venous system using mercury in-Silastic strain-gauge plethysmography (MSGP). Forearm venous capacitance and outflow were examined using five different [7, 14, 21, 28, and 35 mmHg < diastolic blood pressure (DBP)] venous occlusion pressures and after a 5- and 10-min period of venous occlusion. A pressure of 7 mmHg < DBP and a period of 10 min venous occlusion produced the greatest (P < 0.05) venous capacitance and outflow, without altering arterial indexes. Reproducibility of forearm arterial and venous indexes were evaluated at rest and after 5 min of upper arm arterial occlusion at 240 mmHg on three different occasions within 10 days with the interclass correlation coefficient ranging from 0.70 and 0.94. Estimated V(O2) peak correlated with postocclusion arterial inflow (r = 0.54, P = 0.012) and resting venous outflow (r = 0.56, P = 0.016). Finally, handgrip strength was associated with venous capacitance (r = 0.57, P = 0.007) and outflow (r = 0.67, P = 0.001). These results indicate that the examination of forearm vascular function using MSGP is reproducible. Moreover, the data show the importance of careful consideration of the selection of venous occlusion pressure and period when implementing these measures in longitudinal trials. Finally, the associations between fitness and venous measures suggest a link between venous function and exercise performance.

Adult↗

[Cardio- and hemodynamics of dogs during the development of postischemic shock reaction].

Experiments on dogs have shown that tension of peripheral capacitive vessels decreased and development of the blood deposition reaction in the venous part of the vascular bed occurred immediately after beginning of long-ischemized tissue perfusion. This leads to limitation of venous blood return to the heart, decrease of the cardiac output and development of the system hypotension. Lowering in the perfusion coronary pressure induced limitation of the coronary blood flow and inhibition of the myocardial contractility. Indicated constriction of resistive vessels and dilatation of the capacitive ones may be due to an increase of the prostacyclin and thromboxane A2 blood levels. Described disturbances achieved their maximum 3 hours later and were accompanied by arterial hypoxemia, metabolic acidosis and hypercapnia.

6-Ketoprostaglandin F1 alpha↗