Interaction of neuropeptide Y and the sympathetic nervous system in vascular control in man.

Background: There is increasing evidence that neuropeptide Y (NPY) contributes to the autonomic control of the circulation. NPY coexists with noradrenaline in perivascular nerve terminals, may be released during sympathetic stimulation, and is a potent constrictor of the human coronary circulation and other vascular beds. In vitro studies show that NPY can act either directly on vascular smooth muscle or indirectly by modulation of the presynaptic release or the postsynaptic actions of noradrenaline.

On the mechanism of the prolonged action in man of GR32191, a thromboxane receptor antagonist.

Twenty four healthy men were treated with GR32191, a thromboxane receptor antagonist with a long duration of action, in a double blind placebo-controlled crossover study. Platelet aggregation in response to a thromboxane (TX) mimetic (U46619) was studied turbidometrically using platelet rich plasma (PRP) prepared 12 h after dosing (80 mg po) and 1.5 h after a second dose (40 mg po).

Cholesterol:phospholipid ratio is elevated in platelet plasma membrane in patients with hypertension.

The cholesterol:phospholipid ratio was measured in platelet plasma membrane, red blood cell (RBC) membranes, low density lipoprotein (LDL) and whole plasma in patients with primary hypertension and in matched normal controls. The cholesterol:phospholipid ratio was raised in the platelet membrane from hypertensive patients compared with that from normal controls (0.65 +/- 0.

The effect of local converting enzyme inhibition on the dilator response to substance P in the human forearm.

It has been proposed that angiotensin converting enzyme (ACE) may play a part in the metabolism of substance P. Reduced metabolism following treatment with ACE inhibitors may cause accumulation of substance P to produce the adverse effect of cough. It has been shown in this study that, in contrast to angiotensin I and bradykinin, inhibition of local vascular ACE does not interfere with the vascular effects of substance P on forearm resistance vessels when this peptide is infused into the brachial artery of normal volunteers.

Paradoxical effect of bicarbonate on cytoplasmic pH.

The effect of an abrupt rise in bicarbonate concentration on cytoplasmic pH was studied in human platelets suspended in a Tyrode's buffer. Addition of bicarbonate raised extracellular pH but simultaneously caused pronounced cytoplasmic acidification. This effect may be due to combination of bicarbonate with hydrogen ions in extracellular fluid to form carbonic acid, which is converted by carbonic anhydrase to water and carbon dioxide.

Peptide histidine valine: its haemodynamic actions and pharmacokinetics in man differ from those of vasoactive intestinal peptide and peptide histidine methionine.

1. The effects of intravenous and intra-arterial infusion of the peptides derived from prepro-vasoactive intestinal peptide, vasoactive intestinal peptide, peptide histidine methionine and peptide histidine valine, were examined in six healthy volunteers. 2.

Effects of a selective thromboxane receptor antagonist (GR32191B) and of glyceryl trinitrate on bleeding time in man.

1. GR32191B is a potent and selective thromboxane receptor antagonist. Glyceryl trinitrate (GTN) also inhibits platelet function in vitro.

Endothelin is a potent long-lasting vasoconstrictor in men.

Endothelin, a 21-amino acid peptide synthesized by cultured porcine aortic endothelial cells, has recently been identified and shown to produce a potent and prolonged constriction of mammalian blood vessels in vitro. We have studied the effect of local infusion of this peptide on resistance and capacitance vessels of normal volunteers. Infusion of endothelin (5 pmol/min) reduced forearm blood flow by 39 +/- 7% from control observations.

Autoregulation in the human forearm: differences between normal subjects and patients with hypertension.

Autoregulation was assessed in the forearm vascular bed of 16 men with normal arterial pressure and 19 patients with hypertension. The perfusion pressure was varied by changing the height of the forearm above the heart and blood flow was measured by venous occlusion plethysmography. In normal subjects, autoregulation was weak and flow usually increased more than pressure.

Augmentation of sympathetic venoconstriction by angiotensin II in human dorsal hand veins.

The constriction produced by a single deep breath was measured simultaneously in two adjacent hand veins in normal subjects. One vein was infused with saline or angiotensin II; the other acted as a control. A dose of angiotensin II (1 pmol/min) that did produce venous constriction directly significantly augmented the constriction caused by deep breath in eight subjects (P less than .

The potassium channel opening drug cromakalim produces arterioselective vasodilation in the upper limbs of healthy volunteers.

1. The effect of the K+ channel opening drug cromakalim on forearm blood flow during direct infusion into the brachial artery, and on the size of noradrenaline preconstricted hand veins during infusion directly into the vein, was studied in eight healthy volunteers. 2.

Local inhibition of converting enzyme and vascular responses to angiotensin and bradykinin in the human forearm.

1. The function of angiotensin converting enzyme was investigated in twenty-four healthy men. Forearm blood flow was measured under basal conditions and during administration of enalaprilat (a converting enzyme inhibitor) and/or peptide substrates of converting enzyme into the left brachial artery.

The effect of local angiotensin converting enzyme inhibition on the action of atrial natriuretic peptide in the human forearm.

It has been suggested that angiotensin converting enzyme (ACE) may play a role in the metabolism of atrial natriuretic peptide (ANP), and that ANP may interfere with angiotensin-induced vasoconstriction. This has been investigated within the forearm vascular bed during local ANP infusion and ACE inhibition. Six normotensive volunteers were studied, each on two occasions.

Endothelin-1 is a potent long-lasting vasoconstrictor in dog peripheral vasculature in vivo.

Endothelin-1 (ET-1), a 21 amino acid peptide, has recently been identified and shown to produce a potent and prolonged constriction of mammalian blood vessels in vitro. We have studied the effect of local infusion of this peptide on resistance vessels in the hindlimb of the anesthetized greyhound dog. Incremental doses of ET-1 (3-200 pmol/min) were infused into the left femoral artery.

Sympathetically mediated vasoconstriction is augmented by angiotensin II in man.

In order to determine whether angiotensin II may influence sympathetically mediated arteriolar constriction in man, we have examined the effect of angiotensin II, infused directly into the left brachial artery of normal subjects, on the reduction in forearm blood flow produced by a lower-body negative pressure (LBNP) of 15 mmHg. Angiotensin II (320 fmol/min) caused no reduction in blood flow when given alone but significantly augmented the reduction in blood flow in response to LBNP. The same dose of angiotensin II did not affect a similar reduction in forearm blood flow produced by infused noradrenaline (12.

Angiotensin II augments sympathetically induced venoconstriction in man.

1. The constriction produced by a single deep breath was measured simultaneously in two adjacent hand veins in normal volunteers. One vein was infused with angiotensin II (ANG II) while the other acted as a control.

Vascular responses to local atrial natriuretic peptide infusion in man.

1. The effect on skin and muscle blood flow of arterial infusion of atrial natriuretic peptide (ANP) directly into the forearm circulation, and on venous tone of direct infusion into a dorsal hand vein, was studied in normal subjects. 2.

Vasodilatation by calcitonin gene-related peptide and by substance P: a comparison of their effects on resistance and capacitance vessels of human forearms.

A comparison has been made of the effects of the potent vasodilating peptide calcitonin gene-related peptide (CGRP) and substance P (SP) on resistance and capacitance vessels of normal subjects. Brachial artery infusion of 1.25 to 10 pmol/min CGRP and of 0.

Verapamil and bendrofluazide in the treatment of hypertension: a controlled study of effectiveness alone and in combination.

The effects of verapamil and bendrofluazide used singly and in combination were examined in patients with primary hypertension in a patient blind, partly observer blind placebo controlled study of parallel group design; there were ten subjects in each arm of the trial. Verapamil 160 mg twice daily caused supine mean arterial pressure to fall by 21 mmHg; this reduction was significantly greater (p less than 0.05) than that induced by bendrofluazide 5 mg daily which caused a fall of only 10 mmHg.

Is the increased responsiveness to verapamil in the forearm resistance vessels of patients with hypertension a consequence of structural change?

A mathematical model has been developed that relates wall tension in resistance vessels to changes in both distending pressure and flow; the effect of alterations in wall: lumen ratio is taken into account. The model indicates that increased autoregulatory activity in the forearm circulation of patients with primary hypertension could result from an increased response of the vascular smooth muscle to increased intraluminal pressure, but it could be accounted for by an increase in wall:lumen ratio from about 0.2 to 0.