Cyclic Nucleotides and Aggregation in Platelets of Spontaneously Hypertensive Rats

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Abstract

SUMMARY

Abnormalities in the metabolism of cyclic nucleotides have been observed in human as well as in 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 which possesses features in common with vascular smooth muscle. Basal levels of cyclic AMP and cyclic GMP were similar in platelets from SHR (Okamoto) and control (Kyoto-Wistar) rats. Prostaglandin Ei (PGEi) increased cyclic AMP significantly more (in time- and dose-response) in SHR than in control rats, but epinephrine increased cyclic GMP concentrations less in platelets from hypertensive rats. The most significant differences in cyclic nucleotide concentrations were observed in 12-week-old rats; smaller differences were present at the ages of 6 and 24 weeks. Abnormalities in platelet aggregation were observed after addition of the divalent cation ionophore A-23187, a finding compatible either with abnormalities in calcium transport or its function in SHR. Furthermore, although an increase of cyclic AMP was always accompanied by inhibition of aggregation, changes in cyclic GMP concentrations did not correlate with aggregation; the 10-fold increase of cyclic GMP produced by epinephrine was not accompanied by aggregation, whereas the ionophore produced irreversible aggregation in both strains without any change in cyclic GMP concentration. The higher cyclic AMP concentrations observed in SHR in response to PGEi may be due to an increased activity of adenylate cyclase. It is concluded that: (1) abnormalities in aggregation of platelets and metabolism of cyclic nucleotides exist in SHR, and (2) platelets may be a suitable tissue for studies of the regulation of hormonal responsiveness in hypertension.

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