Direct vascular actions of methyclothiazide and indapamide in aorta of spontaneously hypertensive rats

In vitro experiments were designed to assess the inhibitory effect of the t hiazide diuretics methyclothiazide (MCTZ), the hydrochlorothiazide (HCTZ), and the thiazide-related diuretic indapamide (IND) on contractile responses to norepinephrine (NZ) and arginine vasopressin (AVP) of aortic rings From spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats ( WKY). Changes in the tension of aortic ring preparations were measured isom etrically. MCTZ (10(-4) M) induced endothelium-dependent inhibition of the vasoconstrictor responses to NE and AVP only in aortas from SHR, and the ma ximal vasoconstrictive effect of NE and AVP was decreased by 59 +/- 11% and 32.3 +/- 13%, respectively. Indapamide (10(-4) M) also induced endothelium -dependent inhibition of the contractile response to AVP in aortic rings fr om SHR, and the maximal vasoconstrictive effect of AVP was decreased by 33 +/- 5%. In contrast, HCTZ did not inhibit the contractile response to eithe r NE or AVP, even at the highest concentration. This study provides evidenc e that methyclothiazide and indapamide inhibit the contractile response ind uced by norepinephrine and/or arginine vasopressin on SHR aortic preparatio ns via an endothelium-dependent mechanism. (C) 2000 Editions scientifiques et medicales Elsevier SAS.