Amplification of kinin-induced hypotension by nitric oxide synthesis in spontaneously hypertensive rats.
We studied the role of nitric oxide and adrenergic activation in the blood pressure (BP) response to exogenous bradykinin in spontaneously hypertensive rats (SHR) compared with normotensive Wistar-Kyoto rats (WKY). Rats were pretreated with the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME), the alpha-adrenergic receptor antagonist phentolamine together with L-NAME, or phentolamine alone. Sham-injected rats were used as controls. All rats subsequently received bradykinin (3, 6, and 30 micrograms/kg i.v.). Bradykinin induced a concentration-dependent fall in BP in both WKY and SHR (P < .0005). The change in BP was greater in SHR than WKY (P < .0001). BP before bradykinin administration was elevated in the L-NAME group in both strains. In WKY, L-NAME or L-NAME plus phentolamine did not alter the delta BP concentration-response curve to bradykinin (P = NS), whereas in SHR, the delta BP concentration-response curve was attenuated (P < .0048). The attenuation was observed for the two lower bradykinin doses (P < .0005) but not the highest. In SHR, phentolamine alone reduced BP before bradykinin to the same level as in WKY controls, and its delta BP concentration-response curve was not different from that of the normotensive controls or L-NAME and L-NAME plus phentolamine SHR groups. No difference was observed in the duration of the hypotensive response in SHR compared with WKY. The present results confirm that in normotensive rats, the hypotensive effect of bradykinin was mediated by an unknown mechanism other than through the release of nitric oxide. However, in SHR, this mechanism was amplified by additional activation of nitric oxide synthesis. This bradykinin-activated nitric oxide production may be a pressure-induced mechanism to counteract the hypertensive condition.
Bjørnstad-Ostensen
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Department of Physiology, University of Oslo, Norway.
Holte
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HR
Berg
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D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism*; D007022:Hypotension / Q000139:chemically induced*; D007275:Injections, Intravenous; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010646:Phentolamine / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D000317:Adrenergic alpha-Antagonists; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester; D010646:Phentolamine