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.
- SourceAvailable from: Claus Goebel[show abstract] [hide abstract]
ABSTRACT: Cyclic GMP (cGMP) kinase is intimately involved in the regulation of vascular smooth muscle tone. Its tissue concentration was determined in normotensive and hypertensive rats by use of monospecific anti-cGMP kinase antibodies. Hearts of spontaneously hypertensive rats and renovascular (Goldblatt II) hypertensive rats contained half the concentration of cGMP kinase than those of the respective normotensive animals. The increase in blood pressure and the resulting left ventricular hypertrophy were correlated inversely with the left ventricular cGMP kinase concentration. This decrease was specific for the left ventricle and was not observed in other tissues. In addition, the cardiac concentration of cGMP kinase was unchanged in hyperthyroid animals that had comparable left ventricular hypertrophy and mild hypertension. This suggested that in severe renovascular hypertension the decrease in cardiac cGMP kinase concentration is caused by a relative lack of cardiac vessel growth during the development of hypertrophy. In agreement with this conclusion, immunohistochemistry of cardiac cross sections showed that cGMP kinase was exclusively located in cardiac vessels. In support of this localization, the maximal arterial blood flow of heart, liver, skeletal muscle, and kidney correlated excellently with the cGMP kinase content of the respective organ. These results suggest that the cGMP kinase concentration of nonsmooth muscle tissues depends on the amount of organ-specific vascular smooth muscle and may be used as an index for the vascularization of these organs.Circulation Research 12/1989; 65(5):1361-9. · 11.86 Impact Factor
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