Vascular effects of piretanide. Studies on extrarenal action in several animal models

4-Phenoxy-3-(1-pyrrolidinyl)-5-sulfamoyl benzoic acid (piretanide, Arelix) was studied for its vasoactive effects in several experimental models. In rat and rabbit thoracic aorta strips, piretanide dose-dependently attenuated contractions induced by norepinephrine (noradrenaline). When contractions were induced by KCl no concentration response curve could be established. Piretanide inhibited the vasoconstrictor response to norepinephrine and to KCl in the rat mesenteric vascular bed. IC50's of 0.5 mmol/l and 4.9 mmol/l, resp., were calculated. In bovine coronary artery strips piretanide caused a marked relaxation. The vasoconstrictor response to PGE2 in piretanide superfused preparations was attenuated in a concentration related manner. Infusion of piretanide (1 mg X ml-1 X min-1) in the isolated guinea pig heart produced a reversible increase of coronary flow. In both normotensive and spontaneously hypertensive bilaterally nephrectomized pithed rats piretanide caused a significant reduction of diastolic blood pressure. The results contribute to the understanding of the antihypertensive effect of piretanide.