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

Many propeties intrinsic to vascular smooth muscle are altered in hypertension. It is unknown whether these abnormalities are primary traits that many 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 < 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 < 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 segragating 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. These results indicate that blood pressure and the contractile response to ouabain are genetically associated, but blood pressure and the half time for contraction in K⁺-free solution are not. The association between high blood pressure and the augmented ouabain response in SHRSP is not the result of chance selection of allelic variation during inbreeding but rather is the consequence of the same, or closely associated, genetic loci. Therefore, an alteration in the mechanism underlying the vascular contractile response to ouabain may be a contributing factor to hypertension in SHRSP.