Drug-Induced Endothelium-Dependent and -Independent Relaxations in Isolated Resistance Vessels Taken from Simultaneously Hypertensive and Streptozotocin-Diabetic Rats

Abstract

Hypertension and diabetes mellitus often co-exist and both conditions may be expected to cause synergistic vascular damage. Our group has introduced an animal model for simultaneously occurring hypertension and diabetes mellitus by treating spontaneously hypertensive rats with streptozotocin (STZ). We investigated the drug-induced endothelium-independent and -dependent relaxation in isolated mesenteric small arteries (resistance vessels). Concerning the influence of hypertension, the responses to sodium nitroprusside, methacholine, histamine and nifedipine proved unchanged, the vasodilator response to bradykinin was diminished, whereas that to the K(+)-channel opener cromakalim was enhanced. With respect to the influence of STZ-induced diabetes we found that the responses to sodium nitroprusside, methacholine and nifedipine were unchanged, and that to cromakalim was enhanced, also when the preparations were pretreated with glibenclamide. The responses to histamine (STZ WKY versus control WKY) and bradykinin (STZ SHR versus control SHR) proved enhanced in the isolated vessels taken from diabetic animals. These findings suggest that the influence of the diabetic state is more pronounced than that of hypertension. However, our findings do not indicate that either hypertension or diabetes is associated with generalised endothelial damage in the resistance arteries.