PLATELET CAMP AND CGMP IN ESSENTIAL-HYPERTENSION

Vasodilator substances released in the blood vessel wall, such as the endothelium-derived relaxing factor (EDRF) and prostacyclin (PGI2), may participate in the regulation of arterial blood pressure. However, their role in the pathogenesis of human essential hypertension to date remains unclear. For some of these factors affecting vascular smooth muscle cells, blood platelets represent a second target tissue. Thus, EDRF and PGI, inactivate platelets by stimulation of cyclic guanosine-5'-monophosphate (cGMP) and cyclic adenosine-5'-monophosphate (cAMP) synthesis, respectively. In the present study, platelet cAMP (n = 68) and cGMP (n = 60) were determined in a control group of healthy subjects (C) and in 12 patients with untreated essential hypertension (EH). In the control group, platelet cAMP and cGMP content averaged 13.52 +/- 0.38 and 1.48 +/- 0.06 pmol/10(9) platelets and no dependence of either variable on sex or age could be established. Furthermore, cGMP levels were similar in EH as compared to the control group (1.38 +/- 0.11 pmol/10(9) platelets). However, intracellular concentrations of cAMP were significantly lower in EH as compared to C (11.22 +/- 1.37 pmol/109 platelets; P < .01). In addition, we investigated the stimulatory effect on cAMP of the stable PGI, analog iloprost (10-9, 5 . 10(-9), 10(-8) 5 . 10(-8) mol/L) in the platelets of 12 control subjects (C-12) and EH. When the increase in platelet cAMP following iloprost was expressed as the ratio between iloprost stimulated and basal cAMP, no significant differences between C-12 and EH could be determined 11.50 +/- 0.13 (C-12) v 1.40 +/- 0.20 (EH) at 10(-9) mol/L iloprost, 3.51 +/- 0.32 (C-12) V 4.00 +/- 0.67 (EH) at 5 . 10(-9) mol/L iloprost, 11.61 +/- 1.74 (C-12) v 8.46 +/- 1.08 (EH) at 10(-8) mol/L iloprost, and 23.44 +/- 5.10 (C-12) V 16.57 +/- 2.34 (EH) at 5 . 10(-8) mol/L iloprost]. Our data therefore suggest that the reduced cAMP content in platelets of EH subjects may not be due to abnormalities within the target cell but may rather be a consequence of altered adenylate cyclase stimulation, one possible explanation being a decreased production of PGI2. On the other hand, our finding of identical cGMP concentrations in platelets from C and EH subjects does not support the concept that primary hypertension is associated with an abnormal regulation of EDRF synthesis.