Role of endothelium in angiotensin II formation by the rat aorta and mesenteric arterial bed

We investigated the angiotensin II (Ang II)-generating system by analyzing the vasoconstrictor effect of Ang II, angiotensin I (Ang I), and tetradecapeptide (TDP) renin substrate in the abscence and presence of inhibitors of the renin-angiotensin system in isolated rat aortic rings and mesenteric arterial beds with and without functional endothelium. Ang II, Ang I, and TDP elicited a dose-dependent vasoconstrictor effect in both vascular preparations that was completely blocked by the Ang II receptor antagonist saralasin (50 nM). The angiotensin converting enzyme (ACE) inhibitor captopril (36 muM) completely inhibited the vasoconstrictor effect elicited by Ang I and TDP in aortic rings without affecting that of Ang II. In contrast, captopril (36 muM) significantly reduced (80-90 percent) the response to bolus injection of Ang I, without affecting those to Ang II and TDP in mesenteric arteries. Mechanical removal of the endothelium greatly potentiated (70-95 percent) the vasoconstrictor response to Ang II, Ang I, and TDP in aortic rings while these responses were unaffected by the removal of the endothelium of mesenteric arteries with sodium deoxycholate infusion. In addition, endothelium disruption did not change the pattern of response elicited by these peptides in the presence of captopril. These findings indicate that the endothelium may not be essential for Ang II formation in rat mesenteric arteries and aorta, but it may modulate the response to Ang II. Although Ang II formation from Ang I is essentially dependent on ACE in both vessels, our results suggest the existence of an alternative pathway in the mesenteric arterial bed that may play an important role in Ang II generation from TDP in resistence but not in large vessels during ACE inhibition.

The role of angiotensin AT1 receptors in the diuretic, natriuretic, kaliuretic and blood pressure responses induced by angiotensin II activation of the median preoptic nucleus in conscious rats

We determined the effects of two classical angiotensin II (ANG II) antagonists, [Sar1, Ala8]-ANG II and [Sar1, Thr8]-ANG II, and losartan (a nonpeptide and selective antagonist for the AT1 angiotensin receptors) on diuresis, natriuresis, kaliuresis and arterial blood pressure induced by ANG II administration into the median preoptic nucleus (MnPO) of male Holtzman rats weighing 250-300 g. Urine was colected in rats submitted to a water load (5 percent body weight) by gastric gavage, followed by a second water load (5 percent body weight) 1 h later. The volume of the drug solutions injected was 0.5 µl over 10-15 s. Pre-treatment with [Sar1, Ala8]-ANG II (12 rats) and [Sar1, Thr8]-ANG II (9 rats), at the dose of 60 ng reduced (13.7 +/- 1.0 vs 11.0 +/- 1.0 +/- 1.2, respectively), whereas losartam (14 rats) at the dose of 160 ng totally blocked (13.7 +/- 1.0 vs.7.6 +/- 1.5) the urine excretion induced by injection of 12 ng of ANG II (14 rats)...

Effect of glomerulopressin on GFR of rats, role of cyclooxygenase inhibitors and saralasin

En trabajos anteriores se ha demostrado que la glomerulopresina aumenta la filtración glomerular (FG) en sapos, ratas y perros. El efecto de la glomerulopresina es bloqueado por inhibidores de la ciclooxigenasa en varios sistemas. Este trabajo se llevó a cabo con el propósito de estudiar si los inhibidores de la ciclooxigenasa y el bloqueador de los receptores de Ang II, saralasina, impiden el efecto de la glomerulopresina sobre la FG de la rata. Se midió la depuración de inulina en ratas infundidas durante todo el experimento con indometacina o meclofenamato o con saralasina por la vena yugular. Se consideró un período de control durante el cual se infundió Krebs-Ringer-Bicarbonato (KRB) por la arteria femoral y un período experimental durante el cual, en alguns grupos, se cambió la infusión de KRB por la de glomerulopresina. Los inhibidores de la ciclooxigenasa y la saralasina impidieron el aumento de la FG producido por la glomerulopresina. Parece razonable proponer que la glomerulopresina puede aumentar la FG sólo cuando los receptores de la Ang II están libres y que su acción es mediada por la síntesis de prostaglandinas

Effect of Ca++ channel blockers and saralasin on angiotensin II induced contraction in rabbit aortic strip.

To investigate the role of calcium in angiotensin II (A II) induced contractions in rabbit aortic strip, the action of verapamil, nifedipine, cinnarizine and saralasin was studied. The cumulative dose response curves obtained with A II shifted to right with increasing concentrations of all these four agents. The antagonism was noncompetitive. The pD'2 value of saralasin was 8.49 of nifedipine, 8.15 and or verapamil 7.92. Cinnarizine which mainly acts at intracellular site had pD'2 value 5.54. The results indicate that A II induced contractions critically depend on entry of calcium through channels which appear to be closely associated with angiotensin receptors.