Pharmacological analysis of the actions of SKF 82526 on cardiovascular dopamine receptors.
We have performed experiments with SKF 82526, a selective dopamine (DA1) receptor agonist to determine whether this compound would activate either ganglionic and/or central DA receptors. Bilateral hindlimb perfusion was carried out at controlled flow rates and changes in hindlimb perfusion pressure were recorded to evaluate the action of SKF 82526 on vascular resistance in anesthetized dogs. Intracisternal administration of SKF 82526 (10 and 40 micrograms/kg) did not produce any changes in blood pressure, heart rate or hindlimb vascular resistance. When the same doses were administered i.v., SKF 82526 produced hypotension and a decrease in perfusion pressure in the innervated limb, whereas perfusion pressure in the denervated limb was not altered. Intravenous SKF 82526 did not produce any changes in heart rate. When given into the lower abdominal aorta, SKF 82526 caused a dose-dependent decrease in perfusion pressure only in the innervated hindlimb, no significant changes in perfusion pressure occurred in the denervated limb. The hypotensive and the hindlimb vasodilatory actions of SKF 82526 could be antagonized by RS-sulpiride. It was discovered that SCH 23390, a selective DA1 receptor antagonist was most potent in blocking the hypotensive action of i.v. SKF 82526; however, it did not influence the neurogenic hindlimb vasodilation produced by intra-aortic SKF 82526. On the other hand, R-sulpiride, another selective DA1 receptor antagonist significantly antagonized the hypotensive as well as hindlimb vasodilatory actions of SKF 82526. S-sulpiride, a selective DA2 receptor antagonist, was least effective in blocking hypotension and did not influence the hindlimb vasodilatory action.(ABSTRACT TRUNCATED AT 250 WORDS)
Lokhandwala
M F
MF
Watkins
H O
HO
Sabouni
M H
MH
Alkadhi
K A
KA
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D018818:Fenoldopam; D005724:Ganglia / Q000187:drug effects; D006614:Hindlimb / Q000098:blood supply; D008297:Male; D011954:Receptors, Dopamine / Q000187:drug effects*; D013469:Sulpiride / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D001552:Benzazepines; D011954:Receptors, Dopamine; D013469:Sulpiride; D018818:Fenoldopam