Evidence for a visceral smooth muscle abnormality in Okamoto spontaneous hypertension

1. In order to discover whether the changes in reactivity are related to the primary cause of hypertension in spontaneously hypertensive rats (SHR) or are just an adaptation induced by the high arterial blood pressure we tested the contractile response of a visceral smooth muscle from such rats. 2. Longitudinal strips of the fundus from 20 week old male and female SHR and Wistar normotensive (NW) rats were used. Dose-response curves to Ba2+ in SHR strips were displaced to the right as compared to NW rats. Maximal responses were identical. Male SHR fundus strips contracted much more with Sr2+ (SHR: 42+/-3% of maximum response to Ba2+, n=10; NW: 19+/-4%, n=10, P less than 0.01) than NW strips. There was no difference in the response to both BaCl2 and SrCl2 between female SHR and NW fundus strips, and MnCl2 and LaCl3 were relaxant in all cases. 3. Dose-response curves to Ca2+ of depolarized SHR and NW fundus strips were obtained and the effect of diazoxide on Ca2+ contractions was observed. The contractile action of Ca2+ in depolarized preparations was enhanced in both male and female SHR strips. The effect of diazoxide was more marked in SHR strips than in NW fundus strips. 4. SHR fundus smooth muscle shows the same modification of reactivity to Ba2+, Sr2+, Ca2+ and diazoxide that was previously described in arterial smooth muscle. This indicates that the cellular modification responsible for the increase of vascular tonus in SHR is not an adaptive reaction to high blood pressure. The differences between female SHR and male SHR responses are not unexpected, considering the natural evolution of hypertension in Okamoto rats which is milder in the female.