Hipertensión arterial experimental por medio del uso de un bloqueador competitivo de angiotensina II / Experimental arterial hypertension by using an angiotensin II competitive blocker

Se utilizó la saralasina, un bloqueador competitivo de la angiotensina II, con el propósito de incrementar el flujo sanguíneo renal y la tasa de filtración glomerular, para estudiar sus posibles consecuencias tubulares y sobre la presión arterial. Fueron divididas 40 ratas de la línea Wistar, inicialmente normotensas, en 4 grupos: saralasina, supresión, grupos controles corrieron paralelos. Se les realizaron a todos mediciones de variables hemodinámicas sistémicas y renales, así como morfométricas del riñón. Los resultados apoyaron la hipótesis de la participación de la hiperfunción tubular en la génesis de la hipertensión arterial primaria y propusieron un nuevo modelo de hipertensión arterial experimental en ratas

Influência dos subtipos dos receptores da angiotensina II do núcleo paraventricular sobre as respostas fisiológicas induzidas pela angiotensina II injetada na área septal medial / Influence of angiotensin II receptor subtypes of the paraventricular nucleus on the physiological responses induced by angiotensin II injection into the medial septal area

OBJECTIVE: We determined the effects of losartan and PD 123319 (antagonists of the AT1 and AT2 angiotensin receptors, respectively), and [Sar , Ala8] ANG II (a relatively peptide antagonist of angiotensin receptors) injected into the paraventricular nucleus (PVN) on water and 3 percent NaCl intake, and the diuretic, natriuretic, and pressor effects induced by administration of angiotensin II (ANG II) into the medial septal area (MSA) of conscious rats. METHODS: Holtzman rats were used . Animals were anesthetized with tribromoethanol (20 mg) per 100 grams of body weight, ip. A stainless steel guide cannula was implanted into the MSA and PVN. All drugs were injected in 0.5-mul volumes for 10-15 seconds. Seven days after brain surgery, water and 3 percent NaCl intake, urine and sodium excretion, and arterial blood pressure were measured. RESULTS: Losartan (40 nmol) and [Sar , Ala8] ANG II (40 nmol) completely eliminated whereas PD 123319 (40 nmol) partially blocked the increase in water and sodium intake and the increase in arterial blood pressure induced by ANG II (10 nmol) injected into the MSA. The PVN administration of PD 123319 and [Sar , Ala8] ANG II blocked whereas losartan attenuated the diuresis and natriuresis induced by MSA administration of ANG II. CONCLUSION: MSA involvement with PVN on water and sodium homeostasis and arterial pressure modulation utilizing ANGII receptors is suggested

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

Hypertonic saline resuscitation is prevented by intracerebroventricular saralasin but not by captopril

Hypertonic saline resuscitation (HR, 7.5% NaCl, 4 ml/Kg) effectively reverts severe hemorrhage, but a central neural component is probvably involved in the survival response. This experiment examines the role of central angiotensinergic pathways in the hemorrhage-hypertonic resuscitation interaction. Severely bled (43ñ 2 ml/Kg) pentobarbital-anesthetized dogs with chromically imnplanted cerebral ventricular cannulae were resusucitated with 4 ml/Kg 7.5% NaCl, iv 10 min after intracerebroventricular injection of 0.5 ml normal saline (CT), 159 µg saralasin (in 0.5 ml saline, SR), or 10 mg captopril (in 0.5 ml salaine, CP). ALL 10 SR-treated dogs died 2-6 h after HR. Their arterial pressure and cardiac index initially recovered to near pre-hemorrhage levels, but bradually decreased thereafter, base excess remaining ar severe metabolic acidosis levels throughout, al CT-and 8/10CP-treated dogs survived indefinitely,, with near normal arterial pressure, cardiac, index and base excess levels. It is there fore concluded that the inhibition of central angiotensinergic sites with the competitive antagonist saralasin effectively prevents survival after HR, whereas inhibition of angiotensin converting enzyme by captopril in cerebrospinal fluid is virtuallly ineffective