Glandular adenylate cyclase system in genetic hypertension: age-dependent response to catecholamines

The parotid excretion of cAMP was measured in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) in this study. In addition, adenylate cyclase activity in parotid gland tissue was determined. The cAMP excretion rate was increased immediately after isoproterenol infusion. This elevation was more pronounced in young (6-8 weeks) than in older (16-18 weeks) animals, both in WKY and in SHR. These data demonstrate a diminished cAMP response to isoproterenol application with respect to the age of the animals. This could indicate that there is an age-dependent functional alteration of the beta-adrenoceptor-adenylate cyclase complex. In agreement with the results of these in vivo studies, the stimulation of adenylate cyclase activity of the parotid gland by isoproterenol or fluoride was enhanced in young SHR and lowered in old SHR when compared to their normotensive controls of the same age. One may conclude that the sympathetic activity is enhanced in young SHR, and that the beta-adrenoceptor system is hypersensitive to adrenoceptor agonists. This might contribute to the development of hypertension in SHR. Sixteen to eighteen weeks old SHR showed a diminished cAMP output following isoproterenol application when compared to normotensive control rats of the same age. The reduction of the response to isoproterenol stimulation in old SHR seems to be related to a reduced sensitivity to catecholamine stimulation.