ABSTRACT
This study investigated the endothelium-dependent vasorelaxant effects of the essential oil of Ocimum gratissimum (EOOG) in aortas and mesenteric vascular beds isolated from rats. EOOG (3-300 µg/mL) relaxed the tonic contractions induced by phenylephrine (0.1 µmol/L) in isolated aortas in a concentration-dependent manner in both endothelium-containing and endothelium-denuded preparations. This effect was partially reversed by L-NAME (100 µmol/L) but not by indomethacin (10 µmol/L) or TEA (5 mmol/L). In mesenteric vascular beds, bolus injections of EOOG (30, 50, 100, and 300 ng) decreased the perfusion pressure induced by noradrenaline (6 µmol/L) in endothelium-intact preparations but not in those treated with deoxycholate. L-NAME (300 µmol/L) but not TEA (1 mmol/L) or indomethacin (3 µmol/L) significantly reduced the vasodilatory response to EOOG at all of the doses tested. Our data showed that EOOG exerts a dose-dependent vasodilatory response in the resistance blood vessels of rat mesenteric vascular beds and in the capacitance blood vessel, the rat aorta. This action is completely dependent on endothelial nitric oxide (NO) release in the mesenteric vascular beds but only partially dependent on NO in the aorta. These novel effects of EOOG highlight interesting differences between resistance and capacitance blood vessels.
Subject(s)
Aorta, Thoracic/drug effects , Endothelium, Vascular/drug effects , Mesenteric Arteries/drug effects , Mesenteric Veins/drug effects , Ocimum/chemistry , Oils, Volatile/pharmacology , Vasodilator Agents/pharmacology , Animals , Aorta, Thoracic/enzymology , Aorta, Thoracic/metabolism , Cyclooxygenase Inhibitors/pharmacology , Endothelium, Vascular/physiology , In Vitro Techniques , Male , Mesenteric Arteries/enzymology , Mesenteric Arteries/metabolism , Mesenteric Veins/enzymology , Mesenteric Veins/metabolism , Nitric Oxide/antagonists & inhibitors , Nitric Oxide/metabolism , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide Synthase/metabolism , Norepinephrine/antagonists & inhibitors , Norepinephrine/metabolism , Oils, Volatile/chemistry , Potassium Channel Blockers/pharmacology , Rats , Rats, Wistar , Vascular Capacitance/drug effects , Vascular Resistance/drug effects , Vasoconstrictor Agents/antagonists & inhibitors , Vasoconstrictor Agents/pharmacology , Vasodilation/drug effects , Vasodilator Agents/antagonists & inhibitorsABSTRACT
The previous finding that converting enzyme inhibitors (CEIs) potentiate bradykinin (BK), but do not inhibit conversion of angiotensin (ANG) I in isolated vessels, was explored further in the rat perfused mesenteric vascular bed. To investigate whether other peptidases besides angiotensin converting enzyme (ACE) might be involved in CEI-resistant ANG I conversion, synthetic angiotensinogen fragments (1-14, 1-11 and 2-14) were studied. Their vasoconstrictor activities were found to be about 80 times less than that of ANG I, and were not altered by the CEI enalaprilat, indicating that tonin-like enzymes do not play a role in the generation of ANG II by the arterial wall. The hypothesis that BK potentiation by CEI in arteries might be due to a direct effect on the receptors was not supported by the lack of potentiation, by enalaprilat, of the vasorelaxant effect of Lys-Lys-BK (an ACE-resistant BK homologue). Finally, the effect of pH in the perfusing solution on ACE inhibition by enalaprilat was studied. Whereas converting activity decreased with increasing pH in the range 6.8 to 8.1, enalaprilat did not affect the responses to ANG I at pH 7.5 or 7.8, but blocked them at pH 7.1. Our results indicate that arterial ACE shows substrate-specific inhibition and that, at physiological pH, converting activity is resistant to inhibition by CEIs, whose hypotensive action would be due mainly to inhibition of arterial wall kininase activity.