Activity of cyclic GMP-dependent protein kinase in aortae from spontaneously hypertensive rats.

Abstract

It has been suggested that various agents induce relaxation of vascular smooth muscles through guanosine 3',5'-cyclic monophosphate (cGMP) and cGMP-dependent protein kinase (cGMP-PK). In this work, the activity of cGMP-PK was studied in the 30,000 g supernatant from aortae of 4, 6, 8 and 12-week-old spontaneously hypertensive (SHR) and age-matched normotensive Wistar-Kyoto (WKY) rats and also of 4 and 12-week-old normotensive Wistar (W) and Sprague Dawley (SD) rats. At 4 weeks of age, both basal and cGMP-stimulated activity were not different in SHR and WKY rats. Nevertheless, a greater basal activity was measured in W (+50%) and SD (+20%) rats than in SHR, while no difference was observed between stimulated activities. In contrast with observations in the three normotensive rat strains, cGMP-PK activity did not decrease in the aortae supernatant of SHR rats aged 4-12 weeks. This resulted in mean increases of 45 and 30% in the basal and the cGMP-stimulated activity, respectively, in the 12-week-old SHR rats. The abnormal evolution of cGMP-PK activity in the hypertensive strain was already detectable at 4-6 weeks of age. In apparent agreement with observations on protein kinase activity, cGMP binding activity attributable to cGMP-PK was 25% greater in 12-week-old hypertensive rats compared with age-matched WKY rats. These results indicate that in aortae of SHR rats, control of cGMP-PK activity is abnormal early in life.