CALCIUM BLOOD LEVEL MODULATES ENDOGENOUS NITRIC-OXIDE ACTION - EFFECTS OF PARATHYROIDECTOMY IN PATIENTS WITH HYPERPARATHYROIDISM

Platelet cyclic guanosine monophosphate (cGMP) is produced by soluble guanylate cyclase (sGC), the activity of which is modulated by the act ivity of nitric oxide (NO) constitutive synthase (cNOS) which, in turn , is activated by a calcium/calmodulin complex. In primary hyperparath yroidism (H-PTH) an increase in platelet free calcium levels is presen t. In this study we evaluate the platelet cGMP levels, as an expressio n of NO production, in the presence of 3-isobutyl-1-methylxanthine (IB MX) alone (IBMXcGMP) and after stimulation by ionomycine (IONO; IONOcG MP) and sodium nitroprusside (SNP; SNPcGMP), in eight subjects affecte d by H-PTH before and after removal of adenoma. Platelet cGMP levels w ere also measured in seven normal subjects. IBMXcGMP and IONOcGMP were elevated in H-PTH patients compared with normal subjects (1.9 +/- 0.3 vs 0.8 +/- 0.2 fmol/10(6) platelets and 2.7 +/- 0.4 vs 1.4 +/- 0.3; P <0.02 and P<0.05 respectively) but SNPcGMP was unaffected (3.9 +/- 0.6 vs 2.5 +/- 0.5). After parathyroidectomy, blood levels of intact para thyroid hormone (i-PTH), total calcium (t-Ca), IBMXcGMP and IONOcGMP a ll decreased (177.5 +/- 23.9 vs 45.0 +/- 8.8 pg/ml, P<0.005; 6.5 +/- 0 .5 vs 4.6 +/- 0.1 mEq/l, P<0.005, 1.9 +/- 0.3 vs 0.8 +/- 0.2, P<0.005; 2.7 +/- 0.1 vs 1.8 +/- 0.3, P<0.05 respectively), while SNPcGMP was n ot modified (3.9 +/- 0.6 vs 4.3 +/- 0.9). t-Ca and i-PTH were directly correlated with IBMXcGMP (P<0.02, r(s)=0.613; P<0.02, r(s)= 0.576 res pectively) and i-PTH was also correlated with t-Ca (P<0.001, r(s)=0.84 0). In conclusion: (1) levels of IBMXcGMP and IONOcGMP are high in sub jects with H-PTH; (2) after surgery both IBMXcGMP and IONOcGMP decreas e to normal values. As IBMXcGMP expresses basal cGMP and IONOcGMP expr esses the cGMP alter cNOS stimulation, it can be speculated that the i ncrease in NO production could be a mechanism to downregulate the vaso constriction which may be caused by the high calcium levels in smooth muscle cells. After surgery, together with the normalization of calciu m levels, NO production also returned to normal values.