Blood pressure and renal blood flow were monitored in conscious normotensive and two-kidney one-clip Goldblatt hypertensive dogs. Captopril administered IV in a single dose of 0.1 mg/kg to normotensives increased renal blood flow by 26.8 & 7.6% and decreased renal vascular resistance, but did not significantly change blood pressure. Cumulative doses of 0.1 and 0.2 mg/kg increased renal blood flow by 29.9 k 6.5%, and decreased renal vascular resistance and blood pressure significantly. Qualitatively similar changes in blood flow and vascular resistance of the contralateral kidney were obtained in the hypertensives. Blood pressure was reduced by a mean of 11.8 2 4.5 mm Hg, renal blood flow increased by 36.2 2 7.9% by the low dose, blood pressure decreased by 18.4 2 2.7 mm Hg, and renal blood flow increased by 42.3 ? 11.4% by cumulative doses of the inhibitor. Plasma renin activity was increased by captopril in the normotensives and a greater increase in plasma renin activity was obtained in the hypertensives. The hypotensive and renal vasodilator effects of captopril appear to be related to blockade of the influence of the renin-angiotensin system, but another action, potentiation of kinin-induced vasodilatation, may also be involved. 4590037-9727/80/080459-07$0 1 .OO/O

Contractions were elicited by field stimulation and norepinephrine in canine cutaneous arteries in Krebs-bicarbonate and Krebs-Tris media and the effect of angiotensin II, 1 × 10^–7 m, on these responses was determined. The absolute magnitude of the field stimulation responses was much greater in the bicarbonate buffer. Angiotensin caused potentiation in both media of the responses to field stimulation and norepinephrine. In Tris buffer with 5 mM calcium the responses to field stimulation and norepinephrine were greater than in 2.5 mM calcium, however; the degree of potentiation caused by angiotensin was similar at both calcium concentrations. The angiotensin potentiating effect in vitro appears to involve a postsynaptic action of the polypeptide which is not affected by alteration of calcium concentration or the medium.

No abstract

Captopril and teprotide were administered intra-arterially to the kidney and intravenously to inhibit intrarenal and extrarenal converting enzyme (CE), respectively. Captopril was infused at 0.4, 0.8, and 1.6 micrograms . kg-1 . min-1 intra-arterially, and teprotide was given at 0.4 and 0.8 micrograms . kg-1 . min-1 intra-arterially in salt-replete dogs (group 1). Both agents were also given intravenously in the dose of 0.2 mg/kg, known to cause maximal extrarenal CE inhibition. The intra-arterial infusions of the inhibitors had no effect on renal hemodynamics but caused a graded degree of intrarenal CE inhibition. A lesser degree of extrarenal CE inhibition was seen after captopril in these doses. Intravenous administration of captopril and teprotide inhibited extrarenal CE, but only captopril increased renal blood flow (13%). When teprotide was given in a higher dose (group 3, 1.02 mg/kg), it too increased renal blood flow. In salt-deplete dogs (group 2), captopril infused intra-arterially caused a degree of intrarenal CE inhibition comparable with that in the salt-replete dogs but again produced little or no renal hemodynamic changes. When given intravenously in this group, captopril inhibited extrarenal EE and elicited a greater increase in renal blood flow (36%) than in the group 1 dogs. These results indicate that in conscious dogs renal vasodilatation is associated with extrarenal, but not intrarenal, CE inhibition.

1 Vasodilator responses to histamine, bradykinin and sympathetic nerve stimulation were elicited in the perfused paw of dogs treated with bretylium (15-20 mg/kg) and atropine. The H2 -receptor blocking agent, burimamide, when administered in the dose of 5 mg/kg intravenously and 4 mg intra-arterially did not depress significantly these vasodilator responses. The subsequent administration of tripelennamine in the dose of 2.5-5 mg/kg intravenously and 4 mg intra-arterially produced a significant blockade of the response to histamine and reduced the sustained vasodilator response to nerve stimulation. 2 In guanethidine-treated dogs, tripelennamine administered in the same dose following burimamide produced a blockade of the respone to histamine comparable to'that in the bretylium experiments, but decreased only the sustained vasodilator response to stimulation at 1 Hz. When the order of administration of the antihistamines was reversed in another group of guanethidine-treated dogs, tripelennamine had only a slight blocking effect on the response to histamine and did not affect the responses to nerve stimulation. Burimamide exerted a significant blocking effect on the response to histamine, but not to nerve stimulation. Another H2-receptor blocking agent, metiamide, when given after tripelennamine, also had a marked blocking effect on the response to histamine and almost abolished the vasodilator response to 4-methylhistamine, an H2-agonist. Nevertheless, even in the presence of this profound histamine blockade, the sustained vasodilator response to nerve stimulation remained unchanged. 3 In another group of experiments vasoconstrictor responses to exogenous noradrenaline and sympathetic stimulation were initially depressed by burimamide and later returned to control values. Tripelennamine increased these responses by its uptake blocking action. 4 It is concluded that the sustained vasodilator response is not antagonized by a specific antihistaminic action. The decrease in the sustained vasodilator response produced by antihistamines is probably attributable to potentiation of a residual adrenergic vasoconstrictor effect not completely blocked by bretylium.