Treatment of non-insulin-dependent diabetic hypertensive patients with Ca2+ channel blockers is associated with increased platelet sensitivity to insulin.
Insulin influences platelet function by reducing platelet responsiveness to vasoactive agonists. In hypertension these insulin-related inhibitory effects are blunted. The aim of this study was to determine whether platelet sensitivity to insulin is affected after 12 weeks of antihypertensive treatment with calcium channel blockers. Eleven patients with essential hypertension and non-insulin-dependent diabetes were treated with either isradipine or diltiazem. Platelet free calcium concentration was measured spectrofluorometrically in nonstimulated and in angiotensin II (1 nmol/L)-stimulated platelets that had been pre-exposed to insulin (70 microU/mL). Platelets were studied before therapy and after 12 weeks of treatment. Systolic blood pressure and mean arterial pressure decreased significantly during treatment. Both calcium channel blockers equally decreased fasting serum insulin levels (from 138 +/- 2.7 pmol/L before therapy to 106 +/- 9.9 pmol/L after therapy). Results with both calcium channel antagonists were similar and have been pooled. In the pretreatment phase, insulin pre-incubation had no effect on angiotensin II-stimulated intracellular free calcium and responses to angiotensin II were similar in the absence (265 +/- 10.5 nmol/L) and presence of insulin (233 +/- 12.1 nmol/L). After treatment with calcium channel blockers, insulin significantly (P < .001) reduced angiotensin II-induced rise of intracellular free calcium from 214 +/- 7.7 nmol/L (absence of insulin) to 153 +/- 9.3 nmol/L (presence of insulin). Whether these effects are due specifically to calcium channel blockers or whether they are the result of lowering of blood pressure remains unclear. Serum insulin levels were positively correlated with angiotensin II-stimulated increase in intracellular free calcium in platelets pre-exposed to insulin, (r = 0.46; P < .05) suggesting that with increasing levels of insulin resistance, the inhibitory effects of insulin are reduced. This study shows that treatment of non-insulin-dependent diabetic hypertensive patients with these calcium channel blockers reduces hyperinsulinemia and increases sensitivity of platelets to the inhibitory effect of insulin on angiotensin II-stimulated calcium responses.
Touyz
R M
RM
Clinical Research Institute of Montreal, University of Montreal, Quebec, Canada.
Schiffrin
E L
EL
D000804:Angiotensin II / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000097:blood; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications*; D004110:Diltiazem / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000150:complications / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D017275:Isradipine / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D007004:Hypoglycemic Agents; D007328:Insulin; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D004110:Diltiazem; D002118:Calcium; D017275:Isradipine