Differences in acetylcholine- and bradykinin-induced vasorelaxation of the mesenteric vascular bed in spontaneously hypertensive rats of different ages.
The present study examined whether alterations of endothelium-dependent vasorelaxation in spontaneously hypertensive rats (SHR) in response to the endothelium-dependent vasodilators acetylcholine and bradykinin ran parallel. We tried to find out the age at which endothelium-dependent vasorelaxation in response to each agonist became impaired and compared three different groups of SHR aged 7, 21 and 51 weeks. To be able to separate hypertension-induced alterations from age-dependent changes age-matched normotensive Wistar rats were included. Endothelium-dependent vasorelaxation was studied in the mesenteric vascular bed precontracted with noradrenaline, a typical resistance vessel, which showed relaxation to both acetylcholine and bradykinin, and the precontracted thoracic aorta, which only responded to acetylcholine. There were major differences in the agonist-dependent vasorelaxation between bradykinin and acetylcholine in SHR as a function of age. A surprising finding was that acetylcholine-induced relaxation was preserved, even slightly improved not only in young SHR (7 weeks) with developing hypertension but also in adult SHR (21 weeks) with established hypertension, which can be interpreted as a compensatory mechanism. As expected, in old SHR (51 weeks) acetylcholine-induced vasorelaxation was impaired as a consequence of the detrimental effects of long-term hypertension on endothelium. The parallel changes observed with acetylcholine in the mesenteric vascular bed and thoracic aorta provided mutual confirmation. In clear contrast to acetylcholine bradykinin-induced vasorelaxation was already imparied in young SHR with developing hypertension suggesting that bradykinin-induced vasorelaxation is either much more sensitive to detrimental effects of (even slightly) increased blood pressure or, more likely, that there is a basic deficiency in the action of bradykinin in SHR. Thus, our study allows to conclude that impairment of acetylcholine-induced endothelium-dependent vasorelaxation in the mesenteric vascular bed of SHR is a secondary phenomenon developing as a consequence of long-term hypertension while the impaired bradykinin-induced vasorelaxation seems to be a primary phenomenon that could be closely related to the development of hypertension.
Wirth
K J
KJ
Hoechst AG, Frankfurt, Germany.
Linz
W
W
Wiemer
G
G
Schölkens
B A
BA
D000109:Acetylcholine / Q000494:pharmacology*; D000375:Aging / Q000502:physiology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure; D001920:Bradykinin / Q000494:pharmacology*; D066298:In Vitro Techniques; D008643:Mesentery / Q000098:blood supply*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D000109:Acetylcholine; D001920:Bradykinin; D009638:Norepinephrine