Influence of indapamide on isolated rabbit arteries

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Abstract
The effect of indapamide, a high ceiling diuretic, antihypertensive drug, was investigated in helically-cut strips of rabbit cerebral, coronary, renal, mesenteric and femoral arteries and aortae. The addition of indapamide in concentrations higher than 3 .times. 10-5 M relaxed those arterial strips contracted with prostaglandin F2.alpha.; the relaxation being greater in cerebral, coronary and renal arteries. Atropine, propranolol and aminophylline did not reduce the relaxing effect. Hydrochlorothiazide produced fewer incidences of relaxation. Treatment for 20 min with indapamide (3 .times. 10-5 nor higher) significantly attenuated the contractile response of mesenteric arteries to nicotine and tyramine. Contractile responses to transmural electrical stimulation were not reduced but rather potentiated. The dose-response curve of norepinephrine was not significantly affected by indapamide. The contractile response of nictitating membranes of anesthetized cats to stimulation of preganglionic sympathetic nerves was not influenced by indapamide but was abolished by hexamethonium. Apparently, arterial relaxations induced by indapamide are due to a direct action on smooth muscles. Indapamide appears to attenuate the response to nicotine and tyramine by interfering with the mechanism of neuronal amine uptake. This does not involve a ganglionic blockade nor a reduction of the release of norepinephrine from adrenergic nerve terminals.

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