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 vascular 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 microM) produced an endothelium-dependent vasorelaxant effect which was greatly reduced by the B2 receptor antagonist Ac-D-Arg[Hyp3,D-Phe7,Leu8]-bradykinin (1 microM), and was unaffected by the B1 receptor antagonist des-Arg9,[Leu8]-bradykinin (1 microM). The degree of 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 vasoconstriction was unaffected by both B1 and B2 receptor antagonists, and was abolished by 3 microM indomethacin. We conclude that the vasorelaxant effect 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.
Mantelli
L
L
Department of Pharmacology, University of Florence, Italy.
Amerini
S
S
Ledda
F
F
D000375:Aging / Q000378:metabolism; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism; D008729:Methoxamine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D008729:Methoxamine; D001920:Bradykinin