IMPAIRED ENDOTHELIAL RELAXATIONS INDUCED BY AGONISTS AND FLOW IN SPONTANEOUSLY HYPERTENSIVE RAT COMPARED TO WISTAR-KYOTO RAT PERFUSED CORONARY-ARTERIES

The study was designed to compare the effects of agonists and flow on endothelial reactivity in perfused coronary arteries of spontanously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats, To this end, coronary arteries were cannulated at both ends using an arteriograph system. In the absence of flow and under an intraluminal pressure of 30 mm Hg, SHR arteries had larger internal diameters compared to those of WKY rats (275 +/- 10 vs, 239 +/- 7 mu m, p < 0.01), In preparations preconstricted with serotonin HT, concentration-effect curves were constructed by adding acetylcholine or bradykinin in the bath. On the other hand, the effect of a stepwise increase in intraluminal flow (50-450 mu l/min) of physiological salt solution was observed. Agonist-induced dilations were significantly smaller in arteries of SHRs compared to those of WKY rats, Starting flow at the plateau of constriction led to dilations that were also weaker in SHR compared to WKY vessels: 27 +/- 6 vs. 61 +/- 3, p < 0.001, when expressed as percentage of maximal initial constrictions, The maximal dilation induced by flow in SHR arteries was obtained for a greater value of shear stress compared to that determined in WKY preparations: 81 +/- 6 vs. 60 +/- 4 dyn/cm(2), p < 0.01. After endothelium destruction, flow-induced dilation was totally abolished in SHR arteries but only reduced in those of WKY rats, Subsequent additions of sodium nitroprusside induced complete dilations in vessels from both strains, The same protocol was performed in arteries submitted to a perfusion pressure of 90 mm Hg. In these conditions, impairments of agonist- and flow-induced dilations were also evidenced in SHR arteries. These results show that both the endothelium-dependent dilation induced by acetylcholine or bradykinin and the flow-induced dilation are impaired in coronary arteries of SHRs compared to WKY rats. These alterations appear to be due to a deterioration of endothelial cell function in the presence of a normal reactivity of the smooth muscle cells.