Actions of L-NAME and methylene blue on the hypotensive effects of clonidine and rilmenidine in the anesthetized rat.

The antihypertensive mechanism of alpha2-adrenoceptor agonists, such as clonidine and rilmenidine, is not completely elucidated, although it is probably due to reduction of sympathetic tone mediated by stimulation of central alpha2-adrenoceptors. Because activation of alpha2-adrenoceptors on endothelial cells induces release of endothelium-derived relaxing factor (EDRF), we determined whether nitric oxide (NO) release is involved in the antihypertensive action of clonidine and rilmenidine. In chloralose-anesthetised Wistar rats, systolic and diastolic arterial blood pressures were recorded on a polygraph. Intravenous injection of clonidine or rilmenidine (control group) caused a rapid increase of arterial blood pressure. followed by a long-lasting hypotensive effect. The hypotensive effects, estimated as the area enclosed by the decrease in diastolic pressure during the 20 min after clonidine and rilmenidine injections, were 574+/-60 and 410+/-59 mm Hg/min, respectively. The delta decrease in diastolic arterial blood pressure observed 20 min after intravenous injections of clonidine and rilmenidine was 48+/-5 and 34+/-3 mm Hg, respectively. Clonidine and rilmenidine injected 5-10 min after intravenous pretreatment with L-NAME (2 and 1 mg/kg) or methylene blue (10 mg/kg) induced hypotensive effects that were significantly smaller than that observed for the control group. These results suggest that the antihypertensive effects of clonidine and rilmenidine also may be modulated by the NO-cyclic guanosine monophosphate (cGMP) pathway at the level of the central nervous system and/or at the vascular peripheral circulation.

Participation of kinins in the inhibitory action of captopril on acute hypertension induced by L-NAME in anesthetized rats.

The aim of the present study was to investigate the role of bradykinin in the inhibitory action of captopril in hypertension induced by L-NAME in anesthetized rats. Male Wistar rats (260-320 g) were anesthetized with chloralose and arterial blood pressure was recorded with a polygraph pressure transducer. The hypertensive effect of L-NAME was studied in rats pretreated with saline, captopril or HOE 140 plus captopril. The effect of captopril was also studied during the sustained pressor effect of L-NAME. The acute pressor effect of L-NAME (10 mg/kg, i.v.) was significantly reduced by i.v. pretreatment with 2 mg/kg captopril (delta increase of 49 +/- 4.9 mmHg reduced to 20 +/- 5.4 mmHg, P = 0.01). The pressor effect of L-NAME (delta increase of 38 +/- 4.8 mmHg) observed in rats pretreated with captopril and HOE 140 (0.1 mg/kg, i.v.) was not significantly different from that induced by L-NAME in rats pretreated with saline (P = 0.09). During the sustained pressor effect induced by L-NAME (delta increase of 49 +/- 4.9 mmHg) captopril induced a significant (P < 0.05) reduction in arterial blood pressure (delta decrease of 22 +/- 3.0 mmHg). The present results demonstrate that the acute pressor effect of L-NAME is reduced by captopril and this inhibitory effect may be partly dependent on the potentiation of the vasodilator actions of bradykinin.