IN-VITRO PERFUSION STUDIES OF RESISTANCE ARTERY FUNCTION IN GENETIC-HYPERTENSION

To examine the function of resistance-sized arteries in hypertension u nder in vitro conditions that approximate in vivo conditions as much a s possible, we mounted segments of second-order mesenteric resistance arteries from spontaneously hypertensive rats (SHR) and Wistar-Kyoto n ormotensive control rats aged 12 to 13 weeks in a perfusion myograph a nd exposed them to conditions of constant flow and pressure. The endot helial integrity was validated both functionally and histologically. V ascular sensitivity to norepinephrine was examined when the hormone wa s applied either intraluminally or extraluminally and before and after removal of the endothelium. Both endothelium-dependent and -independe nt dilatation was assessed by the intraluminal application of acetylch oline and sodium nitroprusside, respectively. Sodium nitroprusside was applied to arteries after endothelium removal. Arterial responses wer e measured by changes in intraluminal diameter recorded with a video c amera and imaging system. Vessels from SHR demonstrated depressed endo thelium-dependent relaxation but similar endothelium-independent relax ation and greater sensitivity to norepinephrine with both intraluminal and extraluminal application. Removal of the endothelium abolished th e differences in sensitivity to norepinephrine between the two strains . The results demonstrate that resistance arteries from SHR when exami ned under in vitro perfusion display enhanced sensitivity to norepinep hrine due to depressed endothelium-dependent dilatation, and the data suggest that functional modifications in the endothelium may play an i mportant role in hypertensive vascular disease.