A genetic locus (Hyp-2) controlling vascular smooth muscle response in spontaneously hypertensive rats

Aortic vascular smooth muscle from spontaneously hypertensive rats (SHR) is known to respond in vitro to nonphysiologic cations with greater contraction than vascular smooth muscle from certain normotensive control stocks. The pattern of inheritance of the response of aortic rings to cobalt (Co2+) in vitro was determined. The test characteristic utilized was the cobalt response ratio (CRR) defined as the contractile response to 0.6 microM Co2+ divided by the response given by maximal stimulation with 10 microM Co2+. The SHR were crossed with Dahl salt-resistant rats that had been inbred for 21 generations (R/JR strain) to produce F1, F2, and backcross populations. The CRR was 0.90 +/- 0.011 in SHR, 0.74 +/- 0.016 in F1, and 0.38 +/- 0.031 in R/JR. The F1 value was significantly higher than the midparental value indicating partial SHR dominance. The F1 males from reciprocal crosses had similar CRR indicating no sex-linked effect. In the backcross to the R/JR, the CRR showed a bimodal distribution segregating one intermediate type: one R/JR type. In the backcross to the SHR the CRR showed a unimodal distribution. In F2 rats there was a bimodal distribution segregating three intermediate type: one R/JR type. In F2 rats there was a significant (p less than 0.005) blood pressure difference of 9.7 mm Hg between phenotypes. It is concluded that there is an autosomal locus (named "Hyp-2" for hypertension locus number 2) controlling vascular smooth muscle response to Co2+, which exhibits partially dominant inheritance. Alleles at Hyp-2 segregate with an increment in blood pressure.