Effect of dopamine and dopamine-receptor blockade on in vitro renin release, tissue renin content and tissue cyclic AMP content in the rat.
This study evaluated the in vitro renin release, tissue cyclic AMP content (TcAMPc), and tissue renin content (TRC) changes with time, in response to administration of dopamine (DOP) and of the dopamine-receptor blocking agent pimozide (PIM) to renal cortical slices from sodium deficient (SD) rats. Addition of 10(-3)M DOP to the slice preparation resulted in a gradual stimulation of RR with time, which was significantly different from that seen in control samples after 60 min of incubation. In contrast, TcAMPc of the DOP-treated samples was significantly greater than that of controls after 5 min of incubation. At 60 min, mean TRC of DOP-treated samples was greater than that of controls but not significantly. Two PIM doses (10(-8)M and 10(-6)M, whether added alone or together with 10(-3)M DOP to the cortical slice system, significantly increased RR in each instance while simultaneously depressing TcAMP content markedly below that of unstimulated controls at all incubation times examined. Mean TRC of pimozide-treated samples was also lower than that of controls by 60 min. These in vitro data in the SD rat suggest that: 1) stimulation of renin release by DOP is time-dependent and is mediated by a TcAMP-generating mechanism, and 2) the increase in renin release by PIM administration appears to involve pharmacological inactivation of TcAMP-generating pathways and disruption of membrane permeability, leading to uncontrolled RR.
López
G A
GA
Rao
V
V
Mottel
S M
SM
Sheppard
B C
BC
D000818:Animals; D000242:Cyclic AMP / Q000032:analysis*; D004039:Diet, Sodium-Restricted; D004298:Dopamine / Q000494:pharmacology*; D018492:Dopamine Antagonists; D007672:Kidney Cortex / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010868:Pimozide / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D012083:Renin / Q000032:analysis / Q000378:metabolism*; D012964:Sodium / Q000172:deficiency
D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D010868:Pimozide; D012964:Sodium; D000242:Cyclic AMP; D012083:Renin; D004298:Dopamine