Involvement of cyclic-AMP in the hypotensive response to fenoldopam but not to quinpirole in the anaesthetized rat.
1. The objective of the present investigation was to ascertain whether cyclic-AMP acts as a mediator in the hypotensive responses to fenoldopam, a selective dopamine DA-1 receptor agonist and quinpirole, a selective DA-2 receptor agonist, in the anaesthetized rat. 2. The hypotensive response to two doses of fenoldopam (10 and 40 micrograms kg-1, i.v.), when administered in separate groups of animals was reproducible following the administration of saline. 3. Following the i.v. bolus administration of theophylline, IBMX or forskolin, the hypotensive response to fenoldopam (10 micrograms kg-1, i.v.) was significantly potentiated. In addition, the hypotensive response to the higher dose (40 micrograms kg-1, i.v.) was augmented by IBMX. 4. Neither theophylline nor forskolin influenced the hypotensive response to quinpirole. 5. Prior administration of theophylline or forskolin did not alter the hypotensive response to acetylcholine. On the other hand, the hypotensive response to histamine which is reportedly mediated through cyclic-AMP accumulation was significantly potentiated after theophylline administration. 6. These results suggest that cyclic-AMP may be acting as a mediator in the vasodilation and the resultant hypotension following DA-1 receptor activation by fenoldopam. However, the hypotensive response seen with DA-2 receptor activation does not appear to involve cyclic-AMP.
Hegde
S S
SS
Department of Pharmacology, College of Pharmacy, University of Houston, Texas 77004.
Lokhandwala
M F
MF
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D000242:Cyclic AMP / Q000502:physiology*; D004873:Ergolines / Q000494:pharmacology*; D018818:Fenoldopam; D006632:Histamine / Q000494:pharmacology; D008297:Male; D019257:Quinpirole; D051381:Rats; D011919:Rats, Inbred Strains; D013806:Theophylline / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D001552:Benzazepines; D004873:Ergolines; D014665:Vasodilator Agents; D019257:Quinpirole; D006632:Histamine; D013806:Theophylline; D000242:Cyclic AMP; D018818:Fenoldopam; D000109:Acetylcholine; D015056:1-Methyl-3-isobutylxanthine