Cyclic nucleotides and aggregation in platelets of spontaneously hypertensive rats.

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Abstract
Abnormalities in the metabolism of cyclic nucleotides were observed in human and experimental hypertension. This study, conducted in spontaneously hypertensive rats (SHR), established that abnormalities of cyclic nucleotides may be observed in platelets, an easily obtainable tissue with features in common with vascular smooth muscle. Basal levels of cyclic(c)AMP and cGMP were similar in platelets from SHR (Okamoto) and control (Kyoto-Wistar) rats. Prostaglandin E1 (PGE1) increased cAMP significantly more (in time- and dose-response) in SHR than in control rats, but epinephrine increased cGMP concentrations less in platelets from hypertensive rats. The most significant differences in cyclic nucleotide concentrations were observed in 12 wk old rats; smaller differences were present at the ages of 6 and 24 wk. Abnormalities in platelet aggregation were observed after addition of the divalent cation ionophore A-23187, a finding compatible either with abnormalities in Ca transport or its function in SHR. Although an increase of cAMP was always accompanied by inhibition of aggregation, changes in cGMP concentrations did not correlate with aggregation; the 10-fold increase of cGMP produced by epinephrine was not accompanied by aggregation; the ionophore produced irreversible aggregation in both strains without any change in cGMP concentration. The higher cAMP concentrations observed in SHR in response to PGE1 may be due to an increased activity of adenylate cyclase. Abnormalities in aggregation of platelets and metabolism of cyclic nucleotides exist in SHR, and platelets may be a suitable tissue for studies of the regulation of hormonal responsiveness in hypertension.