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.