Effect on rat aortas of Methyclothiazide (cas 135-07-9) and indapamide comparison with hydroclorothiazide

Add time:09/29/2019    Source:infona.pl

Data concerning a vasorelaxant direct action of thiazide diuretics are scarse and controversial. The aim of the present work was to assess and to compare the vascular relaxation induced by indapamide (I), Methyclothiazide (cas 135-07-9) (MT) and hydrochlorothiazide (H).Aortas from spontaneously hypertensive and normotensive rats (SHR and WKY) were mounted in organ bath preparations with a basal tension of 3 g.Firstly, in aortas (with or without fonctional endothelium) precontracted by noradrenaline (NA), 10 - 6 M or arginine vasopressin (AVP), 4.10 - 9 M, a concentration-response curve for vasorelaxation was done with 10 - 9 to 10 - 3 M of I, MT and H. Secondly, after preincubation of aortas by 10 - 4 M of the diuretics studied, a concentration response curve for the vasoconstrictive effect of NA (10 - 9 to 10 - 5 M) and AVP (10 - 1 0 to 10 - 7 M) was performed. Maximal effects and EC 5 0 were compared using variance analysis.Results : vasorelaxation of aortas precontracted by NA or AVP was found only for 10 - 4 M of MT and I and not for H. A 10 - 3 M concentration induced a 88 +/- 3 % (MT) and 52 +/- 8 % (I) decrease of the vasoconstriction elicited by NA 10 - 6 M. MT (10 - 4 M) induced a 94 +/- 4 % decrease of AVP (4 x 10 - 9 M) elicited vasoconstriction.After preincubation by MT (10 - 4 M), the maximal vasoconstrictive effect of NA was decreased (- 59 +/- 11 %). A 40% decrease of the maximal vasoconstriction due to AVP was observed after preincubation by MT (- 20 % with I). EC 5 0 was not significantly altered by the diuretics. These results were observed only in aortas with preserved endothelium and in SHR.Conclusion : a direct vasorelaxant effect may by observed in vitro with MT and I but not with H. This effect is at least partially endothelium-dependent and is at best observed in SHR.

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