Role of vasopressin in the cardiovascular effects of LY171555, a selective dopamine D2 receptor agonist: Studies in conscious Brattleboro and Long-Evans rats

Academic Article

Abstract

  • To elucidate the role of central and peripheral arginine vasopressin (AVP) in the cardiovascular action of LY171555 in conscious rats, we have examined the effects of LY171555 on mean arterial pressure, heart rate, plasma AVP and catecholamine levels in conscious, congenitally AVP-deficient Brattleboro (DI) rats and Long-Evans (LE) control rats. Administration of LY171555 (1 mg/kg i.v.) increased heart rate without altering mean arterial pressure in DI rats but increased both mean arterial pressure and heart rate in LE rats. After pretreatment with domperidone, LY171555 induced both a pressure response and a tachycardia in DI rats. Domperidone pretreatment enhanced the pressor action of LY171555 and attenuated the LY171555-induced tachycardia in LE rats. After pretreatment with phenoxybenzamine, LY171555 induced a depressor and bradycardic response that could be blocked by pretreatment with domperidone in DI rats. Pressor and bradycardic responses to LY171555 were attenuated by phenoxybenzamine pretreatment in LE rats. LY171555 administration increased plasma norepinephrine and epinephrine levels in both DI and LE rats but increased plasma AVP only in LE rats. The vasopressor effect of the alpha-1 adrenoceptor agonist phenylephirne was significantly attenuated in DI rats compared with LE rats, whereas the pressor action of angiotensin II was similar in both groups. These results suggest 1) that the pressor action of LY171555 in conscious LE rats is mediated by an increase in plasma AVP and by activation of sympathetic outflow through the central D2 dopaminergic system but not through the central vasopressinergic system and 2) that the lack of pressor action of LY171555 in DI rats may be due not only to the genetic defect of AVP but also to vascular hyporesponsiveness to alpha-1 adrenergic stimulation. Further, the tachycardic action of LY171555 in conscious LE rats is dependent on activation of sympathetic outflow but not on increased circulating AVP levels or increased activity of the central vasopressinergic system.
  • Authors

    Author List

  • Nagahama S; Ann HS; Chen YF; Lindheimer MD; Oparil S
  • Start Page

  • 143
  • End Page

  • 151
  • Volume

  • 242
  • Issue

  • 1