Genetic basis for altered vascular responses to ouabain and potassium-free solution in hypertension

Abstract

Many properties intrinsic to vascular smooth muscle are altered in hypertension. It is unknown whether these abnormalities are primary traits that may contribute to the etiology of hypertension or whether these vascular differences between the hypertensive and normotensive strains are inherited independently of genetic factors that predispose to hypertension. To determine if genetic factors responsible for the predisposition for hypertension may be the same as or linked to genetic factors determining a specific vascular response, adult stroke-prone spontaneously hypertensive rats (SHRSP), normotensive Wistar-Kyoto (WKY) rats, and progeny of genetic crosses of SHRSP and WKY rats (F1, F2, F1 X WKY, F1 X SHRSP) were studied. Rats were killed and helical aortic strips were mounted in a tissue bath for isometric force recording. Contractile responses to 10(-3) M ouabain (expressed as a percent of force generated to a maximal depolarizing stimulus) were greater in aortas from SHRSP (90 +/- 9%) compared with aortas from WKY rats (38 +/- 5%, P less than 0.05). The half time for contraction in K+-free solution was more rapid in aortas from SHRSP (21 +/- 4 min) when compared with aortas from WKY rats (48 +/- 4 min, P less than 0.05). A significant positive correlation between blood pressure (tail-cuff method) and the contractile response to 10(-3) M ouabain was observed in the segregating F2 progeny. In contrast, no correlation between blood pressure and the half time for contraction in K+-free solution was observed in the segregating F2 progeny.(ABSTRACT TRUNCATED AT 250 WORDS)