Arterial hypertrophy and pressor responsiveness during development of hypertension in spontaneously hypertensive rats

In contrast to studies in isolated blood vessels, results from whole-animal studies are ambiguous regarding differences in pressor responsiveness between spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats, possibly related to the measurement of blood pressure instead of total peripheral resistance (TPR) and to differences in compensatory mechanisms.

We evaluated responses of blood pressure and TPR to two doses of the alpha 1-agonist phenylephrine during the development of hypertension and cardiovascular hypertrophy in SHR aged 8-26 weeks compared with age-matched WKY rats before and after ganglionic blockade. At 16 weeks of age more-complete dose-response curves to the alpha 1-agonist methoxamine were also constructed.

Over the age range studied, the SHR developed marked hypertension, related to a significant rise in TPR, and concomitantly significant cardiac hypertrophy, as well as hypertrophy of the mesenteric arterial bed. The blood pressure responses to phenylephrine were diminished in the SHR compared with the WKY rats at all ages studied, but this effect was significant only in the absence of ganglionic blockade. TPR responses were significantly less in the SHR than in the WKY rats, both with and without concomitant ganglionic blockade. In contrast, both blood pressure and TPR responses to low doses, but not higher doses, of methoxamine were enhanced in the SHR compared with the WKY rats.

These results indicate that the development of hypertension in SHR in vivo is associated with variable changes in blood pressure and TPR responses to alpha 1-receptor stimulation, depending on the alpha 1-agonist employed.