Effect of vasoactive peptides on prostacyclin synthesis in man

The Journal of Physiology

Collier

et al. 1989

102

SUMMARY1. 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. Blood flow was compared in the two arms.2. Enalaprilat had no effect on basal blood flow. The concentration of enalaprilat in venous blood from the control arm was low, and plasma renin activity was not increased, indicating that systemic inhibition of converting enzyme did not occur.3. Effects of angiotensin and of bradykinin, administered intra-arterially, were limited to the infused arm. Enalaprilat (13 nmol min-1) inhibited converting enzyme in the infused arm, in which it caused approximately a 100-fold reduction in sensitivity to angiotensin I, while having no effect on the vasoconstriction caused by angiotensin II. Enalaprilat increased vasodilatation caused by bradykinin.4. Aspirin, an inhibitor of cyclo-oxygenase, did not inhibit vasodilatation caused by bradykinin whether infused alone or with enalaprilat. indicating that these responses are not mediated by prostaglandins.5. We conclude that under basal conditions neither conversion of angiotensin I to angiotensin II nor degradation of bradykinin determines resistance vessel tone in the human forearm. Converting enzyme may affect vascular tone in situations in which intravascular concentrations of peptides are increased over those present under basal conditions.

Section: Mechanism Of Bradykinin-induced Vasodilatationmentioning

confidence: 99%

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

Benjamin

The Journal of Physiology

Collier

et al. 1989

102

“…Plasma prostaglandins were assayed using capillary column gas chromatography/electron capture mass spectrometry (Barrow et al, 1986.…”

Section: Assaysmentioning

confidence: 99%

Differential effect of aspirin on thromboxane and prostaglandin biosynthesis in man.

Ritter

Doktor

et al. 1989

Brit J Clinical Pharma

1 Effects of a single intravenous dose of aspirin (600 mg) on bradykinin-stimulated prostaglandin (PG) and on thromboxane (TX) biosynthesis were determined in nine healthy male volunteers. Plasma concentrations of 6-oxo-PGF,1ll and 13,14-dihydro-15-oxo-PGF2a were measured in samples obtained during repeated 10 min intravenous infusions of bradykinin before and up to 6 h after the dose of aspirin. TXB2 was measured in serum from blood allowed to clot at 370 C. 2 Aspirin inhibited bradykinin stimulated PG and platelet TX biosynthesis 0.5 h after the dose. Serum TXB2 remained low, whereas PG synthesis recovered within 6 h. 3 Effects of intravenous sodium salicylate (600 mg) were studied identically in eight subjects. Prostanoid biosynthesis was not inhibited. 4 Biosynthesis of prostacyclin and TXA2 under basal conditions was studied in eight subjects by measuring 2,3-dinor-6-oxo-PGF1,, and 2,3-dinor-TXB2 in hourly urine samples obtained during and after intravenous infusion of aspirin and, on a separate occasion, of vehicle.5 Aspirin infusion reduced urinary excretion of both metabolites > 90%, but excretion of 2,3-dinor-6-oxo-PGF1a recovered more rapidly than did that of 2,3-dinor-TXB2. 6 We conclude that cyclo-oxygenase is rapidly synthesised in bradykinin-responsive tissues in vivo and that this reflects similarly rapid enzyme biosynthesis in tissues that produce PGI2 under basal conditions. Keywords thromboxane A2 prostacyclin prostaglandin metabolites bradykinin aspirin

“…It causes vasodilation in human resistance vessels [4] and veins [5]. Bradykinin stimulates biosynthesis of vasodilator prostaglandins in human subjects [6,7], but pharmacologic inhibition of prostaglandin biosynthesis has little effect on its haemodynamic effects in man [8][9][10]. In some species it releases the endothelium derived relaxing factor (EDRF) [11] now known to be nitric oxide (NO) [12,13] or closely related to it, and some at least of its vasodilator effect in man is probably mediated by EDRF/NO [14].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of bradykinin‐induced vasodilation in human forearm vasculature by icatibant, a potent B2‐receptor antagonist.

Chowienczyk

Brett

et al. 1994

Brit J Clinical Pharma