Antihypertensive activity of indolepyruvic acid: a keto analogue of tryptophan.
We studied the effect of indole-3-pyruvic acid (IPA) on systolic blood pressure of normotensive, spontaneously hypertensive, DOCA + salt hypertensive, and Grollman hypertensive rats. Experiments were also carried out in order to investigate whether IPA may influence the development of hypertension in spontaneously hypertensive rats. Age-matched normotensive, spontaneously hypertensive, DOCA + salt hypertensive, and Grollman hypertensive rats treated with N-methylglucamine, were used as controls. Acute oral (up to 50 mg/kg) and intravenous (5 mg/kg) administration of IPA did not change systolic blood pressure in any models of hypertension. By contrast, a repeated administration of IPA (100 mg/kg/day, by oral gavage for 10 days) significantly decreased systolic blood pressure in all models of hypertension, while it elicited no significant effect in normotensive rats. Moreover, when IPA was given daily to 5-week-old spontaneously hypertensive rats for 7 weeks, it partially inhibited the development of hypertension. In addition, chronic administration of IPA caused enhanced levels of tryptophan and 5-hydroxyindoleacetic acid in the cortex and diencephalon. Brainstem serotonin content in both normotensive and spontaneously hypertensive rats was also enhanced by IPA treatment. Our results suggest that IPA lowers blood pressure in different rat models of hypertension and this effect seems to be correlated with an increase in cerebral serotonin metabolism.
Squadrito
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Institute of Pharmacology, School of Medicine, University of Messina, Italy.
Sturniolo
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Trimarchi
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Campo
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GM
De Luca
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Gorini
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Caputi
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AP
D000818:Animals; D000959:Antihypertensive Agents; D001794:Blood Pressure / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D003900:Desoxycorticosterone; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology; D006978:Hypertension, Renovascular / Q000503:physiopathology; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008536:Meglumine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D014364:Tryptophan / Q000031:analogs & derivatives*
D000959:Antihypertensive Agents; D007211:Indoles; D003900:Desoxycorticosterone; C008122:indol-3-yl pyruvic acid; D008536:Meglumine; D014364:Tryptophan