Reactivity of aorta and mesenteric microvessels to drugs in spontaneously hypertensive rats: role of the endothelium.

Abstract

The response to vasoactive agents of microvessels in situ and aortae in vitro was studied in normal and spontaneously hypertensive rats (SHR). Noradrenaline (NA) was equally effective in evoking a constrictor response of mesenteric microvessels in normal rats and SHR. The vasodilator response to acetylcholine (ACH), as endothelium-dependent relaxing agent, was lower in SHR microvessels whereas isoproterenol, papaverine, agents which are partially dependent on endothelium, and sodium nitroprusside, an endothelium-independent vasodilator, induced similar responses in control rats and SHR. Median effective concentrations and maximal responses to NA obtained in isolated SHR aortae, with or without endothelium, were similar to those obtained in their respective controls. NA-precontracted aortae with intact endothelium were less responsive to ACH in SHR than in controls. The relaxant response of the preparations was lost after endothelial cell removal in both groups. Sodium nitroprusside evoked similar relaxing effect in SHR and control NA-precontracted aortae. Isoproterenol-induced responses were potentiated in SHR-precontracted aortae, with or without endothelium. Removal of the endothelium diminished isoproterenol-induced relaxation, both in controls and SHR. With submaximal concentration of papaverine there was no difference between SHR aortae with or without endothelium and control aortae with endothelium. Control aortae without endothelium relaxed less than control aortae with endothelium and SHR aortae with or without endothelium. The rate of relaxation after papaverine was altered in aortae without endothelium isolated from SHR or control rats. These results indicate that the endothelium of SHR is altered. This could explain its decreased response to ACH. It is suggested that smooth muscle cells develop a compensatory mechanism that increases the response of agents that mobilize cAMP, such as papaverine and isoproterenol.