Enhanced depressor effect of bromocriptine in the DOCA/NaCl hypertensive rat.
To elucidate the role of the dopaminergic system in the maintenance of hypertension in the deoxycorticosterone acetate (DOCA)/NaCl hypertensive rat, the responses of mean arterial pressure (MAP), plasma norepinephrine (NE), epinephrine (E), and prolactin (PRL) to intravenous (iv) administration of bromocriptine, a dopamine agonist, and hexamethonium bromide, a ganglion blocker, were examined in conscious, unrestrained 4-wk DOCA/NaCl hypertensive rats. Bromocriptine was administered to adrenomedullectomized (ADMX) rats to assess the role of the adrenal medulla in its depressor effect. Bromocriptine (50, 250, and 500 micrograms/kg) and hexamethonium (3 and 30 mg/kg) caused dose-dependent decreases in MAP that were greater in DOCA/NaCl rats than in uninephrectomized controls. Basal plasma NE, E, and PRL were significantly higher in DOCA/NaCl rats than in controls. Bromocriptine (500 micrograms/kg iv) decreased plasma PRL to undetectable levels and increased plasma E significantly without changing NE levels in DOCA/NaCl and uninephrectomized control rats. In ADMX rats bromocriptine (500 micrograms/kg iv) decreased MAP, PRL, and NE without affecting E levels. These results suggest that the depressor response to bromocriptine could be related to inhibition of sympathetic outflow without participation of the adrenal medulla. The hyperprolactinemia and enhanced depressor response to bromocriptine observed in DOCA/NaCl animals suggest that the dopaminergic system might be altered in this model of hypertension.
Nagahama
S
S
Chen
Y F
YF
Oparil
S
S
D000313:Adrenal Medulla / Q000502:physiology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001971:Bromocriptine / Q000494:pharmacology*; D003864:Depression, Chemical; D003900:Desoxycorticosterone / Q000633:toxicity*; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists; D004837:Epinephrine / Q000097:blood; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced*; D008297:Male; D009638:Norepinephrine / Q000097:blood; D011388:Prolactin / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D012965:Sodium Chloride / Q000633:toxicity*
D018492:Dopamine Antagonists; D006584:Hexamethonium Compounds; D001971:Bromocriptine; D018738:Hexamethonium; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D011388:Prolactin; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine