Differential effects of captopril on regional haemodynamic responses to angiotensin I and bradykinin in conscious rats.

Abstract

1. Conscious, Long Evans rats were chronically instrumented with pulsed Doppler flow probes and intravascular catheters to allow regional haemodynamic (coeliac, mesenteric and hindquarters vascular beds) responses to i.v. bradykinin to be assessed in the absence and presence of captopril and of ganglion blockade (with mecamylamine). 2. Bradykinin (3 nmol kg-1, i.v. bolus) had no effect on mean arterial blood pressure, although it caused hyperaemic vasodilatation in the coeliac, mesenteric and hindquarters vascular beds. Following administration of captopril at a dose (28 nmol kg-1) which had no effect on responses to angiotensin I, the hypotensive and coeliac and mesenteric vasodilator responses to bradykinin were enhanced. However, there was a temporal dissociation between these events indicating that changes in cardiac output must have been contributing to the changes in mean arterial blood pressure. 3. Captopril at a higher dose (280 nmol kg-1) caused reversible inhibition of the pressor and coeliac and mesenteric vasoconstrictor effects of angiotensin I, but the inhibition of the mesenteric vascular responses was significantly less than that of the coeliac vascular responses. Under the same conditions, the mesenteric vasodilator effects of bradykinin were less enhanced than the coeliac vasodilator effects, consistent with greater inhibition of angiotensin-converting enzyme (i.e., kininase II) in the coeliac than in the mesenteric vascular bed. But, since the hypotensive action of bradykinin was markedly enhanced in these circumstances, the possibility existed that baroreflex responses influenced the haemodynamic effects of bradykinin. However, assessment of the haemodynamic changes following bradykinin administration(bolus or infusion) in the presence of ganglion blockade showed that only the hindquarters vasodilator response to bradykinin was enhanced, while the coeliac and mesenteric vasodilator responses were diminished. Thus, additional factors must have been influencing the latter responses.4. The results show that inhibition of angiotensin-converting enzyme (kininase II) can have differential effects on the regional haemodynamic responses to angiotensin I and bradykinin. The results provide a striking illustration of our previous assertion that the measurement of arterial blood pressure alone cannot provide sufficient information to allow interpretation either of the effects of vasoactive substances,or of the influence of drugs thereupon.