Abstract

Nitric oxide (NO) induces vasorelaxation and inhibits platelet aggregation via an increase of the second messenger cGMP, synthesized by soluble guanylyl cyclase in vascular smooth muscle cells and platelets, respectively. To test whether the acute hemodynamic effects of an NO-donor are associated with changes of platelet cGMP, in 15 essential hypertensives grade I-II (age 46±3 yrs) isosorbide dinitrate (ISDN) was infused at 1 microgr/kg/min for 30 min. Platelet (PLT) and plasma cGMP, systolic and diastolic arterial pressure (SAP, DAP, sphygmo), heart rate (HR), stroke volume index (SVI, impedance cardiography) were measured and total peripheral resistance index (TPRI) calculated at baseline and after ISDN. TABLE shows means±sem; * p<0.05

PLT cGMPSAPDAPHRSVITPRI
pM/109 pltmmHgmmHgb/minml/m2dyn.s.cm-5.m2
Basal7.0 ± 0.5156 ± 699 ± 467 ± 238 ± 1.33809 ± 227
ISDN7.4 ± 0.5138 ± 6°95 ± 469 ± 333 ± 1.5°4060 ± 253
PLT cGMPSAPDAPHRSVITPRI
pM/109 pltmmHgmmHgb/minml/m2dyn.s.cm-5.m2
Basal7.0 ± 0.5156 ± 699 ± 467 ± 238 ± 1.33809 ± 227
ISDN7.4 ± 0.5138 ± 6°95 ± 469 ± 333 ± 1.5°4060 ± 253
PLT cGMPSAPDAPHRSVITPRI
pM/109 pltmmHgmmHgb/minml/m2dyn.s.cm-5.m2
Basal7.0 ± 0.5156 ± 699 ± 467 ± 238 ± 1.33809 ± 227
ISDN7.4 ± 0.5138 ± 6°95 ± 469 ± 333 ± 1.5°4060 ± 253
PLT cGMPSAPDAPHRSVITPRI
pM/109 pltmmHgmmHgb/minml/m2dyn.s.cm-5.m2
Basal7.0 ± 0.5156 ± 699 ± 467 ± 238 ± 1.33809 ± 227
ISDN7.4 ± 0.5138 ± 6°95 ± 469 ± 333 ± 1.5°4060 ± 253

The decrease of arterial pressure was secondary to SVI decrements, as both HR and TPRI were unchanged. PLTcGMP changes were inversely related to SAP decrements (r=-0.69, p<0.01). No relationship was present between PLT and plasma cGMP, which tended to decrease after ISDN (from 8.6±1.0 to 7.8±0.9 nM/l).

These data indicate that in EH patients the acute venodilating effect of an NO-donor is directly related to its stimulating effect of cGMP in platelets.

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