Genetic association of hypertension and vascular changes in stroke-prone spontaneously hypertensive rats

Isolated tail arteries from stroke-prone spontaneously hypertensive rats (SHRSP) exhibit oscillatory contractile activity in response to norepinephrine, whereas those from normotensive Wistar-Kyoto rats (WKY) do not. To determine whether the norepinephrine-induced oscillations are related to high blood pressure or to separable genetic differences between strains, the response to norepinephrine was studied in adult SHRSP, WKY, and progeny of genetic crosses of SHRSP and WKY (F₁, F₂, F₁ x SHRSP, F₁ x WKY). Helical tail artery strips were mounted in a tissue bath for isometric force recording. Rats were classified as responders if oscillatory activity in the presence of 1.8 x 10^-7 M norepinephrine exceeded 250 mg/10 min (milligrams of force amplitude during a 10-minute interval). The blood pressures (mm Hg ± SEM; tail cuff method) and percentage of rats exhibiting norepinephrine-induced oscillations were as follows: WKY: 109 ± 3, 0%; F₁: 129 ± 4, 0%; F₂: 150 ± 4, 38%; F₁ x WKY: 137 ± 3, 9%; F₁ x SHRSP: 188 ± 7, 71%; SHRSP: 207 ± 7, 100%. The distribution of the frequency of animals with oscillatory activity among the progenies was consistent with the hypothesis that a single gene locus determines the observed difference in oscillatory activity between the WKY and SHRSP strains. The allele from the SHRSP that determines the activity phenotype is recessive to the allele contributed by the normotensive WKY strain. In the segregating F₂ progeny, the blood pressure of the responders was higher than that of the nonresponders (161 ± 6 vs 144 ± 4 mm Hg; p < 0.05). We conclude that the genetic locus that controls the norepinephrine-induced oscillatory activity may contribute to the observed blood pressure difference between WKY and SHRSP.