Bromocriptine decreases blood pressure of spontaneously hypertensive rats without affecting the adrenomedullary synthesis of catecholamines.
Because of controversial data on the role of adrenomedullary catecholamines (CA) in the hypertension of spontaneously hypertensive rats (SHR) and in the hypotensive action of bromocriptine, we studied the effect of chronic bromocriptine treatment on blood pressure (BP), adrenal CA synthesis, tissue CA, and urinary excretions of CA and their metabolites in SHR. We found that the hypertension of 12-week-old SHR (systolic BP, 181 +/- 13 mm Hg) was reduced to 123 +/- 8 mm Hg when they received bromocriptine between 4 and 12 weeks of age (2 X 600 micrograms/kg/day, intraperitoneally). Although the urinary epinephrine (E) and the synthesis of adrenal norepinephrine (NE), E, and dopamine (DA), as well as the tissue content of CA in adrenals, heart, and kidney, remained unchanged after bromocriptine treatment, the urinary NE and DA excretions were lower in bromocriptine-treated SHR than in sham-treated SHR (NE, 2.7 +/- 0.3 versus 4.2 +/- 0.3 nmol/24 h in control SHR; DA, 18.7 +/- 1.6 versus 28.2 +/- 2.2 nmol/24 h in control SHR). In SHR, bromocriptine treatment did not affect the previously observed selectively increased adrenal turnover and synthesis of DA or the urinary excretions of normetanephrine (NM), dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT), or homovanillic acid (HVA). The results suggest that the bromocriptine-induced decrease of BP in SHR is not mediated by changes in adrenomedullary CA and that bromocriptine decreases the BP of SHR without affecting the previously observed increased adrenal DA release of SHR. Thus, other central or peripheral dopaminergic agonist actions of bromocriptine bypassing the adrenal medulla must be considered in the hypotensive action of the drug.
D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001971:Bromocriptine / Q000494:pharmacology*; D002395:Catecholamines / Q000096:biosynthesis* / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis; D004837:Epinephrine / Q000096:biosynthesis; D007668:Kidney / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000096:biosynthesis; D051381:Rats; D011918:Rats, Inbred SHR
D002395:Catecholamines; D001971:Bromocriptine; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine