Reference

Sympatho-inhibitory properties of various AT1 receptor antagonists

Some chemicals with cas registry numbers like 138402-11-6 and 144701-48-4 are also used. Sympatho-inhibitory properties of various AT1 receptor antagonists. Balt, Jippe C.; Mathy, Marie-Jeanne; Pfaffendorf, Martin; van Zwieten, Peter A. (Department of Pharmacotherapy, Academic Medical Center, University of Amsterdam, Amsterdam 1105 AZ, Neth.). Journal of Hypertension, 20(Suppl. 5), S3-S11 (English) 2002 Lippincott Williams & Wilkins. CODEN: JOHYD3. ISSN: 0263-6352. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) It is well known that angiotensin II (Ang II) can facilitate the effects of sympathetic neurotransmission. In the present study, using various exptl. models, we investigated the inhibitory effects of several Ang II subtype 1 receptor (AT1) antagonists on this Ang II-induced facilitation. We compared the sympatho-inhibitory potencies of the AT1 blockers with their resp. potencies regarding inhibition of the direct vasoconstrictor effects of Ang II. In the isolated mesenteric artery, we investigated the effects of Ang II in the presence and absence of losartan, irbesartan and telmisartan on stimulation-induced vasoconstrictor responses. In the pithed rat, we studied the effect of AT1 blockade on the sequelae of elec. stimulation of the thoracolumbar sympathetic outflow (presynaptic AT1 blockade) as well as on dose-response curves elicited by exogenous Ang II (postsynaptic AT1 blockade). Addnl., we compared the sympatho-inhibitory of irbesartan in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. In the isolated mesenteric artery, Ang II (10 nM) significantly enhanced stimulation-induced vasoconstrictor responses. The enhancement could be antagonized in a concn.-dependent manner by losartan (1 nmol/l to 1 mmol/l), irbesartan (0.1 nmol/l to 0.1 mmol/l) and telmisartan (0.01 nmol/l to 0.01 mmol/l). The sympatho-inhibitory potency was telmisartan > irbesartan > losartan. In the pithed normotensive rat, the stimulation-induced increase in diastolic blood pressure (DBP) as well as the Ang II-elicited DBP response were dose-dependently reduced by all the AT1 receptor blockers investigated. The order of potency with respect to sympatho-inhibition was eprosartan > valsartan = candesartan = embusartan = telmisartan > losartan > irbesartan (comparison of doses which at 2 Hz reduced DDBP by 20 mmHg, differences significant at P < 0.05). The order of potency regarding inhibition of the Ang II-induced DBP increase was candesartan > embusartan = valsartan = eprosartan = telmisartan > irbesartan > losartan (comparison of the antagonist concn., in the presence of which twice the agonist concn. is needed to cause the same effect [pA2 values], differences significant at P < 0.05). In the pithed SHR and the normotensive WKY rat the sympatho-inhibitory potency of irbesartan did not differ significantly between both strains. It can be concluded that all AT1 receptor antagonists appear to possess sympatho-inhibitory properties, which may be of potential interest in the treatment of hypertension and heart failure. Our findings suggest differences in pre- and postsynaptic inhibition between the various compds., since for eprosartan and losartan the sympatholytic doses and postsynaptic inhibitory doses differed far less than for the other AT1 receptor antagonists. .

Angiotensin II type 1 receptor blocker irbesartan ameliorates vascular function in spontaneously hypertensive rats regardless of oestrogen status

Angiotensin II type 1 receptor blocker irbesartan ameliorates vascular function in spontaneously hypertensive rats regardless of oestrogen status. Riveiro, Alberto; Mosquera, Alejandro; Alonso, Manuela; Calvo, Carlos (Hypertension Unit, Department of Medicine, Hospital Clinico Universitario, Santiago de Compostela, Spain). Journal of Hypertension, 20(7), 1365-1372 (English) 2002 Lippincott Williams & Wilkins. CODEN: JOHYD3. ISSN: 0263-6352. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Angiotensin II type 1 (AT1) receptor overexpression may play a decisive role in endothelial dysfunction during estrogen deficiency in spontaneously hypertensive rats (SHRs). Similarly, exaggerated prodn. of angiotensin II and enhanced expression of AT1 receptor have been reported in vessels of SHRs compared with normotensive rats. To test the hypothesis that antihypertensive treatment with the AT1 receptor antagonist, irbesartan, could not only decrease blood pressure but also ameliorate endothelial dysfunction assocd. with both hypertension and estrogen deficiency. Ovariectomized and sham-ovariectomized SHRs were treated with 50 mg/kg irbesartan per day, administered with chow for 30 wk. Sham-ovariectomized and ovariectomized rats receiving no treatment were used as control groups. At the end of the treatment period, the vascular reactivity of aortic rings was studied. In the irbesartan-treated groups, vasoconstriction induced by Nw-nitro-L-arginine Me ester (L-NAME) was increased and the response to phenylephrine exhibited greater potentiation in the presence of L-NAME, demonstrating a greater availability of basal nitric oxide in these groups. In addn., chronic treatment with irbesartan similarly enhanced the responsiveness of aortic rings from ovariectomized or sham-ovariectomized rats to acetylcholine and sodium nitroprusside. Incubation with indomethacin did not significantly alter acetylcholine-and sodium nitroprusside-induced relaxations in the irbesartan-treated rats. 138402-11-6 which is the cas registry number of one of substances is just one of reagents here. However, relaxations induced by acetylcholine and sodium nitroprusside in aortic rings from non-treated rats were significantly greater in the presence of indomethacin. Our data suggest that irbesartan enhances basal nitric oxide availability and ameliorates vascular relaxations in SHRs, by decreasing the prodn. of cyclooxygenase-dependent contracting factors in smooth muscle cells, regardless of estrogen status. .