Cyclic nucleotides and platelet aggregation in hypertensive rats with ectopic pituitary tumor

The transplantable pituitary tumor MtT-F4 secretes several pituitary hormones in Fisher rats, resulting in severe cardiovascular disease with a mineralocorticoid type of hypertension and hyperlipidemia. The mineralocorticoid-dependent hypertension possesses particular characteristics in humans and animals. It was of interest to study cyclic nucleotides and platelet aggregation in the Fisher rat with an MtT-F4 tumor in order to evaluate the type of abnormalities in this form of hypertension. The effect of administration of an anti-hyperlipidemic agent (clofibrate) was also evaluated. The animals bearing the tumor showed anomalies of platelet aggregation induced by the divalent cation ionophore A 23187, in that there was an apparent enhanced change in shape and a decreased rate of aggregation. Although the basal concentrations of cyclic nucleotides were normal, as were the increases in cyclic GMP induced by epinephrine, cyclic AMP concentrations increased less (about 2.7-fold) in response to PGE1 than in control Fisher rats (about 6-fold). A decreased stimulation of adenylate cyclase activity by PGE1 was observed in platelets of tumor-bearing rats. The administration of clofibrate to sham-operated animals somewhat lowered the increase of cyclic AMP in response to PGE1. In tumor-bearing animals, clofibrate considerably reduced plasma lipids, blood pressure and the degree of abnormalities in platelet aggregation and cyclic AMP in platelets. Thus, the abnormalities of platelet aggregation and regulation of cyclic nucleotides in the mineralocorticoid-type of hypertension induced by MtT-F4 were opposite to those found previously in spontaneous hypertension in rats. Hyperlipidemic and hypertensive rats with MtT-F4 tumor may provide a useful model for the study of the relatioship between hyperlipidemia and hypertension.