Pharmacological evidence for the activation of potassium channels as the mechanism involved in the hypotensive and vasorelaxant effect of dioclein in rat small resistance arteries.
The hypotensive and vasorelaxant effect of dioclein in resistance mesenteric arteries was studied in intact animals and isolated vessels, respectively. In intact animals, initial bolus administration of dioclein (2.5 mg kg(-1)) produced transient hypotension accompanied by an increase in heart rate. Subsequent doses of dioclein (5 and 10 mg kg(-1)) produced hypotensive responses with no significant change in heart rate. N(G)-nitro-L-arginine methyl ester (L-NAME) did not affect the hypotensive response. In endothelium-containing or -denuded vessels pre-contracted with phenylephrine, dioclein (5 and 10 mg kg(-1) produced a concentration-dependent vasorelaxation (IC(50)=0.3+/-0.06 and 1.6+/-0.6 microM, respectively) which was not changed by 10 microM indomethacin. L-NAME (300 microM) produced a shift to the right. Dioclein was without effect on contraction of vessels induced by physiological salt solution (PSS) containing 50 mM KCl and the concentration dependence of dioclein's effect on phenylephrine induced contraction was shifted to the right in vessels bathed in PSS containing 25 mM KCl. Tetraethylammonium (10 mM) and BaCl(2) (1 mM) increased the IC(50) for dioclein-induced vasorelaxation without affecting the maximal response (E(max)). Charybdotoxin (100 nM), 4-aminopyridine (1 mM) and iberiotoxin (100 nM) increased the IC(50) and reduced the E(max). Apamin (1 microM) reduced the E(max) without affecting the IC(50). Dioclein produced a hyperpolarization in smooth muscle of mesenteric arteries with or without endothelium (7.7+/-1.4 mV and 12.3+/-3.6 mV, respectively). In conclusion dioclein lowered arterial pressure probably through a decrease in peripheral vascular resistance. The underling mechanism implicated in the vasorelaxant effect of dioclein appears to be the opening of K(Ca) and Kv channels and subsequent membrane hyperpolarization.
Côrtes
S F
SF
Laboratório de Farmacologia Cardiovascular, Departamento de Farmacologia - ICB. Universidade Federal de Minas Gerais 31270 - 901, Belo Horizonte - Brazil.
Rezende
B A
BA
Corriu
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C
Medeiros
I A
IA
Teixeira
M M
MM
Lopes
M J
MJ
Lemos
V S
VS
D015761:4-Aminopyridine / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D017609:Barium Compounds / Q000494:pharmacology; D018999:Charybdotoxin / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D003243:Consciousness; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D044950:Flavanones; D005419:Flavonoids / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D007022:Hypotension / Q000139:chemically induced*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D019789:Tetraethylammonium / Q000494:pharmacology; D013997:Time Factors; D014655:Vascular Resistance; D014664:Vasodilation / Q000187:drug effects*
D000700:Analgesics; D017609:Barium Compounds; D002712:Chlorides; D004791:Enzyme Inhibitors; D044950:Flavanones; D005419:Flavonoids; D010455:Peptides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C094747:dioclein; C024986:barium chloride; D018999:Charybdotoxin; D001030:Apamin; D019789:Tetraethylammonium; D011189:Potassium Chloride; C064719:iberiotoxin; D015761:4-Aminopyridine; D019001:Nitric Oxide Synthase; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester