Vascular Effects Of Bradykinin Research Articles

Triphasic vascular responses to bradykinin in the mesenteric resistance artery of the rat

The vascular effects of bradykinin were studied in rat perfused mesenteric vascular beds with active tone. Bolus injections of bradykinin (1–1000 pmol) but not des-Arg 9-bradykinin (bradykinin B 1 receptor agonist) induced triphasic vascular responses: the initial sharp vasodilation followed by transient vasoconstriction and subsequent gradual vasodilation. The triphasic vascular responses to bradykinin were abolished by FR 172357 (3-bromo-8-[2,6-dichloro-3-[ N-[( E)-4-( N, N-dimethylcarbamoyl) cinnamidoacetyl]- N-methylamino]benzyloxy]-2-metylimidazo[1,2- a]pyridine) (bradykinin B 2 receptor antagonist, 0.1 μM). Endothelium removal with sodium deoxycholate and N w-nitro- l-arginine (300 μM) abolished the bradykinin-induced initial sharp vasodilation. Indomethacin (0.5 μM) and seratrodast (thromboxane A 2 receptor antagonist, 0.5 and 5 μM) abolished the bradykinin-induced second vasoconstriction. The bradykinin-induced third vasodilation was abolished by capsaicin (1 μM) and calcitonin gene-related peptide (CGRP)-(8–37) (CGRP receptor antagonist, 0.5 μM). These findings suggest that the bradykinin-induced initial sharp vasodilation is endothelium dependent, that endogenous thromboxane A 2 is involved in the second vasoconstriction, and that the third slow vasodilation is produced by activation of capsaicin-sensitive CGRP-containing nerves.

Metalloendopeptidases EC 3.4.24.15 and EC 3.4.24.16: potential roles in vascular physiology

The zinc metalloendopeptidases EC 3.4.24.15 (EP 24.15) and EC 3.4.24.16 (EP 24.16) are closely related ubiquitous enzymes, which have well-defined in vitro activities in generation and degradation of a range of specific peptide targets. Despite this, little is known regarding their roles in whole animal physiology. One of the peptides degraded by these enzymes in vitro is bradykinin, a mediator with potent effects on the vasculature at both systemic and local levels. This review summarises the work that has examined the role of EP 24.15/24.16 in regulation of the vascular effects of bradykinin in vivo. This work was made possible by the development of a specific stable inhibitor of these enzymes, JA-2. Use of this inhibitor has shown that EP 24.15/24.16 are capable of regulating responses induced by exogenous bradykinin. This effect was observed at a systemic level with an increase in the hypotensive effect of intravenous bradykinin. Further work is required to determine whether these enzymes also regulate bradykinin produced endogenously.

ATP is involved in myocardial and vascular effects of exogenous bradykinin in ejecting guinea pig heart.

It has recently been reported that bradykinin induces selective left ventricular (LV) relaxation in isolated guinea pig hearts via the release of nitric oxide. Exogenous bradykinin also induces vasodilation, which is only partly due to nitric oxide release. In the present study we investigated the role of adenyl purines on these bradykinin-induced effects. Isolated ejecting guinea pig hearts were studied. LV pressure was monitored by a 2-Fr micromanometer-tipped catheter. ATP concentrations were measured using a luciferin-luciferase assay. Bradykinin (1 and 100 nM) caused a progressive acceleration of LV relaxation together with a transient increase in coronary flow. These effects were inhibited by the nonselective P(2) purinoceptor antagonist suramin (1 microM, n = 6) but were unaffected by the selective P(2x) purinoceptor antagonist pyridoxal phosphate 6-azophenyl-2',4'-disulfonic acid (1 microM, n = 6). These myocardial and vascular effects of bradykinin were associated with increased ATP levels in coronary effluent. These data suggest that the selective enhancement of LV relaxation and rise in coronary flow induced by exogenous bradykinin involve endogenous ATP and the subsequent stimulation of P(2) purinoceptors.

Vascular Effects of Bradykinin and Sodium Nitroprusside During Pregnancy in the Rat

The vascular reactivity of pregnant rats to vasodilator agents was determined by measuring their in vivo and in vitro responses to bradykinin (BK) and sodium nitroprusside (SNP) at mid-term (9 days) and at term-pregnancy (21 days), by comparison to non-pregnant rats. In conscious, unrestrained and catheterized rats, the dose-response curves of bolus SNP and BK injections were progressively shifted to the left in both groups of pregnant rats, but this increased sensitivity reached significance only in term-pregnant rats. The baroreceptor reflex influence on blood pressure response to these agents was similar in the three groups of rats and cannot explain the increased response to the vasodilators observed. The in vitro vasorelaxation produced by SNP on NE (6 × 10-6 M) pre-contracted mesenteric bed was not changed in mid-term and term-pregnant rats. In contrast, the vasorelaxant responses of BK were significantly reduced in the pre-contracted mesenteric bed of term-pregnant animals in comparison to non-preg...

Influences of low sodium diets on vascular effects of bradykinin and on bradykinin receptors in the uterine smooth muscle in the rats.

A low sodium diet for 7 days in the rat induced an enhancement of the vascular effects of bradykinin, determined as the blood pressure response, by 56%. However, this enhancement reverted after 28 days of a low sodium diet. A sustained increase in the number of uterine smooth muscle bradykinin receptors during low sodium diets was observed, 1.3 times of the control on the 7th day and 1.7 times on the 28th day. No change in binding affinity was found in any of the studies. These results suggest that the vascular effects of bradykinin after low sodium diets may be regulated by homeostatic mechanisms via the change in the number of vascular smooth muscle bradykinin receptors at subcellular levels, and that the number of uterine smooth muscle bradykinin receptors may be affected by sodium status per se.

Mechanism of the Protective Effect of Angiotensin-Converting Enzyme Inhibition in Hemorrhagic Shock

SummaryAnesthetized cats subjected to hemorrhage were treated with captopril, a CEI (0.5 μg/kg/hr) alone or in conjunction with angiotensin II (10 μg/kg/hr). Angioten-sin II administration significantly reduced survival time (110 vs 64 min) and lowered superior mesenteric artery flow (SMAF) immediately after reinfusion (8.5 vs 2.2 ml/kg/ min). These results suggest that blockade of angiotensin II formation is a prominent aspect of the beneficial actions of captopril in hemorrhage. Furthermore, captopril potentiated the vascular effects of bradykinin at normal blood pressures but not in hemor-rhagic hypotension. In the same experiments, captopril blocked the vascular effects of angiotensin I at both pressures. Thus, bradykinin potentiation is not essential for the beneficial actions of captopril in hemorrhagic shock, since hypotension abolishes the bra-dykinin-potentiating effects of captopril. Reduction of angiotensin II formation appears to be a major mechanism of captopril action in prolonging survival ...