Hypotensive action of 5-HT receptor agonists in the vitamin B6-deficient hypertensive rat.
Feeding a vitamin B6-deficient diet to rats causes a moderate hypertension. The blood pressure responses to 5-HT1A receptor agonists were studied in conscious vitamin B6-deficient hypertensive rats. They were all effective in lowering blood pressure with the following rank order of potency: 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) > flesinoxan > 5-methylurapidil > urapidil. The putative 5-HT1A receptor antagonist spiroxatrine by itself, did not have any effect on the blood pressure at the doses used (0.01-1 mumol/kg). However, dose dependently, it antagonized the hypotensive effect of flesinoxan and urapidil. The alpha 1-adrenoreceptor antagonist prazosin, on prior treatment, did not change the hypotensive effect of either flesinoxan or urapidil. The alpha 2-adrenoreceptor agonist clonidine dose dependently (0.01-0.1 mumol/kg) reduced blood pressure. This effect of clonidine was unaffected by spiroxatrine, but was dose dependently antagonized by the alpha 2-adrenoreceptor antagonist yohimbine. Binding studies with [3H]8-OH-DPAT indicated that the affinity and Bmax of 5-HT1A receptors was increased in vitamin B6-deficient hypertensive rats. The results suggest that decreased synthesis of 5-HT in brain regions and the consequent alterations in 5-HT receptors in the vitamin B6-deficient rats may be the underlying cause of the hypertension seen in these animals.
Lal
K J
KJ
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Dakshinamurti
K
K
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012257:Riboflavin Deficiency / Q000503:physiopathology*; D012701:Serotonin / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D015016:Yohimbine / Q000494:pharmacology
D000959:Antihypertensive Agents; D010879:Piperazines; D017366:Serotonin Receptor Agonists; C057446:5-methylurapidil; D015016:Yohimbine; D012701:Serotonin; C056895:flesinoxan; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C015568:urapidil; D003000:Clonidine