Calcium antagonism and the vasorelaxation of the rat aorta induced by rotundifolone.
The vasorelaxing activity of rotundifolone (ROT), a major constituent (63.5%) of the essential oil of Mentha x villosa, was tested in male Wistar rats (300-350 g). In isolated rat aortic rings, increasing ROT concentrations (0.3, 1, 10, 100, 300, and 500 microg/ml) inhibited the contractile effects of 1 microM phenylephrine and of 80 or 30 mM KCl (IC50 values, reported as means +/- SEM = 184 +/- 6, 185 +/- 3 and 188 +/- 19 microg/ml, N = 6, respectively). In aortic rings pre-contracted with 1 microM phenylephrine, the smooth muscle-relaxant activity of ROT was inhibited by removal of the vascular endothelium (IC50 value = 235 +/- 7 microg/ml, N = 6). Furthermore, ROT inhibited (pD2 = 6.04, N = 6) the CaCl2-induced contraction in depolarizing medium in a concentration-dependent manner. In Ca2+-free solution, ROT inhibited 1 microM phenylephrine-induced contraction in a concentration-dependent manner and did not modify the phasic contractile response evoked by caffeine (20 mM). In conclusion, in the present study we have shown that ROT produces an endothelium-independent vasorelaxing effect in the rat aorta. The results further indicated that in the rat aorta ROT is able to induce vasorelaxation, at least in part, by inhibiting both: a) voltage-dependent Ca2 channels, and b) intracellular Ca2+ release selectively due to inositol 1,4,5-triphosphate activation. Additional studies are required to elucidate the mechanisms underlying ROT-induced relaxation.
Guedes
D N
DN
Laboratório de Tecnologia Farmacêutica, Universidade Federal da Paraíba, João Pessoa, PB, Brazil.
Silva
D F
DF
Barbosa-Filho
J M
JM
Medeiros
I A
IA
D000818:Animals; D001011:Aorta / Q000187:drug effects; D002118:Calcium / Q000037:antagonists & inhibitors*; D004730:Endothelium, Vascular / Q000187:drug effects; D020128:Inhibitory Concentration 50; D008297:Male; D027541:Mentha; D039821:Monoterpenes / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010938:Plant Oils / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology*
D039821:Monoterpenes; D010938:Plant Oils; D014665:Vasodilator Agents; C467828:rotundifolone; D002118:Calcium