BRADYKININ-INDUCED VASODILATION IS CHANGED TO A VASOCONSTRICTOR RESPONSE IN VESSELS OF AGED NORMOTENSIVE AND HYPERTENSIVE RATS

The vascular response to bradykinin was investigated in mesenteric vas cular bed preparations preconstricted with methoxamine, obtained from 2- and 18-month old normotensive (WKY) and spontaneously hypertensive (SHR) rats. In preparations from young normotensive rats bradykinin (1 nm-10 mu M) produced an endothelium-dependent vasorelaxant effect whi ch was greatly reduced by the B2 receptor antagonist Ac-D-Arg[Hyp(3), D-Phe(7),Leu(8)]-bradykinin (1 mu M), and was unaffected by the B1 rec eptor antagonist des-Arg(9),[Leu(8)]-bradykinin (1 mu M). The degree o f vasodilation was similar in preparations from age-matched SHR rats. In vessels obtained from old animals bradykinin induced an endothelium -independent vasoconstrictor response; this effect was more pronounced in preparations from SHR than in those from WKY rats. The vasoconstri ction was unaffected by both B1 and B2 receptor antagonists, and was a bolished by 3 mu M indomethacin. We conclude that the vasorelaxant eff ect of bradykinin in vessels of young animals is due to stimulation of B2 receptors. This vasodilating response can be converted by aging to a vasoconstriction and is probably due to the release of a prostanoid product; moreover it is more pronounced in spontaneously hypertensive animals.