Chronic dietary administration of tryptophan prevents the development of deoxycorticosterone acetate salt induced hypertension in rats.
Hypertension developed within 3 to 5 weeks in uninephrectomized rats administered deoxycorticosterone acetate (DOCA) at a dose of 850 micrograms X kg-1 X day-1 via Silastic tubes and given isotonic saline to drink. Chronic dietary administration of tryptophan (25 and 50 g/kg of food) to DOCA-treated rats reduced their exaggerated intake of NaCl solution and attenuated the elevation of blood pressure induced by treatment with DOCA alone. Treatment with tryptophan also protected against the reduction in urinary concentrating ability during a 24-h dehydration that is characteristic of DOCA-treated rats. Other tests assessed the responsiveness to the beta-adrenergic agonist, isoproterenol. These included measurement of drinking and heart rate following acute administration of isoproterenol. The characteristically depressed drinking and chronotropic responses of DOCA-treated rats to acute administration of isoproterenol were unaffected by tryptophan. Responsiveness to angiotensin II (AII) was also tested by assessment of dipsogenic and metabolic responses to acute administration of AII. The increased drinking and tail skin temperature responses to administration of AII, characteristic of DOCA-treated rats, were reduced in a graded fashion by treatment with graded doses of tryptophan. The specific binding of AII to its receptors in membranes form the diencephalon of the brain was increased by treatment with DOCA but was returned to control level by concomitant treatment with tryptophan. The content of serotonin in the mesencephalon of the brain was not changed significantly by treatment with tryptophan, but the content of 5-hydroxyindole acetic acid in the same region increased significantly, suggesting that turnover of serotonin was increased by chronic treatment with tryptophan. The cardiac hypertrophy characteristic of treatment with DOCA was attenuated significantly by chronic treatment with tryptophan, while the low, resting plasma renin activity of the DOCA-treated group was unchanged. These results suggest that tryptophan provides significant protection against the development of DOCA-induced hypertension, polydipsia, polyuria, and cardiac hypertrophy in rats. It also reduces the hyperresponsiveness to treatment with AII, possibly by decreasing the specific binding of AII to its receptors. It also appears to increase the turnover of serotonin in the brain. Whether either one or all of these is responsible for the antihypertensive effect of tryptophan remains for further study.
D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000378:metabolism; D003900:Desoxycorticosterone / Q000037:antagonists & inhibitors*; D004231:Diuresis / Q000187:drug effects; D004334:Drug Administration Schedule; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000517:prevention & control*; D007545:Isoproterenol / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism; D012881:Skin Temperature / Q000187:drug effects; D013894:Thirst / Q000187:drug effects; D014364:Tryptophan / Q000008:administration & dosage*
D000804:Angiotensin II; D012701:Serotonin; D003900:Desoxycorticosterone; D014364:Tryptophan; D007545:Isoproterenol