Blunted pressor responsiveness to quinpirole, a specific dopamine D2 receptor agonist, in conscious deoxycorticosterone acetate/NaCl hypertensive rats is related to atrial natriuretic peptide release.
Our previous studies have demonstrated: 1) that i.v. quinpirole (LY171555), a selective dopamine D2 receptor agonist, has a dose-dependent pressor effect in conscious rats which is mediated by activation of sympathetic outflow and vasopressinergic activity, and 2) that the activity of central dopaminergic neurons is reduced in deoxycorticosterone acetate (DOCA)/NaCl hypertensive rats. To elucidate the role of central and peripheral dopaminergic systems in the pathogenesis of DOCA/NaCl hypertension, we examined the effects of quinpirole on mean arterial pressure, heart rate, plasma norepinephrine, epinephrine, arginine vasopressin and atrial natriuretic peptide (ANP) in conscious 4-week-old DOCA/NaCl hypertensive and normotensive control rats. Quinpirole (1 mg/kg i.v.) increased mean arterial pressure in both groups, but the pressor response was attenuated in DOCA/NaCl rats. Paradoxically, quinpirole-induced increments in plasma norepinephrine, epinephrine and arginine vasopressin were greater in DOCA/NaCl rats. In addition, quinpirole induced a 2-fold increase in plasma ANP (P less than .01) in both DOCA/NaCl and control rats. Pretreatment with domperidone (2.5 mg/kg i.v.), a peripherally acting dopamine D2 antagonist, enhanced the maximum pressor response to quinpirole in both groups, restored the quinpirole-induced pressor response to control levels in the DOCA/NaCl rats and blocked the stimulatory effect of quinpirole on ANP release in both groups. These data indicate that peripheral dopamine D2 receptors modulate ANP secretion in the rat. The observation that the quinpirole-induced increment in plasma ANP was enhanced in DOCA/NaCl rats supports the hypothesis that the blunted pressor response to quinpirole in this model is related to enhanced ANP release.
Chen
Y F
YF
Department of Medicine, University of Alabama at Birmingham.
Jin
H K
HK
Paul
R
R
Nagahama
S
S
D000818:Animals; D001127:Arginine Vasopressin / Q000097:blood; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects*; D003900:Desoxycorticosterone; D004294:Domperidone / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D004837:Epinephrine / Q000097:blood; D004873:Ergolines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000097:blood; D019257:Quinpirole; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*
D004873:Ergolines; D011954:Receptors, Dopamine; D001127:Arginine Vasopressin; D019257:Quinpirole; D003900:Desoxycorticosterone; D004294:Domperidone; D009320:Atrial Natriuretic Factor; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine