Analysis of responses to angiotensin II in the mouse

Abstract

Responses to angiotensin II (Ang II) were investigated in anaesthetised CD1 mice. Injections of Ang II caused dose-related increases in systemic arterial pressure that were antagonised by candesartan. Responses to Ang II were not altered by PD 123319. At the lowest dose studied (20 µg/kg i.v.), the inhibitory effects of candesartan were competitive, whereas at the highest dose (100 µg/kg i.v.), the dose-response curve for Ang II was shifted to the right in a non-parallel manner. The inhibitory effects of candesartan were selective and were similar in animals pretreated with enalaprilat to reduce endogenous Ang II production. Pressor responses to Ang II were not altered by propranolol, phentolamine or atropine, but were enhanced by hexamethonium. Increases in total peripheral resistance were inhibited by the AT 1 -receptor antagonist (ARB) but were not altered by AT 2 -receptor, alpha-or beta-receptor antagonists. These results suggest that pressor responses to Ang II are mediated by AT 1 -receptors, are buffered by the baroreceptors, are not modulated by effects on AT 2 -receptors, and that activation of the sympathetic nervous system plays little role in mediating rapid haemodynamic responses to the peptide in anaesthetised mice. IntroductionAngiotensin II (Ang II) plays an important role in regulating arterial pressure, sodium, and water balance.1 Ang II binds with high affinity to AT 1 -and AT 2 -receptors.2-4 Ang II-induced increases in systemic arterial pressure and the release of aldosterone are mediated by AT 1 -receptors, whereas less is known about the role of the AT 2 -receptor in the regulation of cardiovascular function.2-4 AT 1 -receptors are widely distributed, and AT 1 -antagonists are effective in the treatment of hypertension and congestive heart failure.5 AT 2 -receptors are highly expressed in the foetus and are downregulated with time, suggesting that they are involved in growth and development.

ATP-binding cassette transporter Abcg2 lineage contributes to the cardiac vasculature after oxidative stress

“…This chemical was chosen as a simple and effective agent for generating cellular oxidative stress levels without concomitant tissue injury. To date, there has not been a suitable alternative for an in vivo oxidative stress model without tissue injury (1,3,6,8,12,29,32,38). As reported in previous studies (2, 4) using PQ to generate high-level ROS to mimic disease systems, we observed a significant increase in oxidative stress markers in cardiac tissue within hours of treatment.…”

Angiotensin II Directly Increases Endothelial Calcium and Nitric Oxide in Kidney and Brain Microvessels In Vivo With Reduced Efficacy in Hypertension

“…Most transgenic mouse studies using AT 1a , AT 1b , and AT 2 receptor knockout animals showed that AT 1a R is the receptor that drives most physiological responses to angiotensin II including blood pressure control, 48 , 49 although other studies underscored the tissue‐specific roles of AT 1b R. 50 The lack of hypertension in VEC specific AT 1a R knock out mice 51 , 52 is somewhat conflicting with our results which can be explained by the more pronounced role of this vasodilator mechanism in stressed disease conditions compared with healthy conditions. Angiotensin II–induced VEC calcium responses were exclusively mediated via the AT 1 R, in agreement with earlier studies showing that acute vasoconstrictor responses to angiotensin II were mediated by actions at the AT 1 R, and that acute responses are not counterbalanced by opposing effects on the AT 2 R. 53 Other studies provided additional confirmation regarding the key role of the AT 1 R and that the AT 2 R does not contribute significantly to the observed angiotensin II–induced VEC calcium elevations or other vascular responses 54 , 55 including in brain microvessels. 56 Our results are also in agreement with the previous demonstration of AT 1 R‐mediated activation of VEC calcium signaling and NO production by angiotensin II, 18 , 19 which has been previously attributed to AT 2 R functions.…”

Age- and Gender-Related Differences in Renal Vascular Responses to Angiotensin II in Rats: The Role of the Mas Receptor

“…First, the present study exhibited the increment of MAP and RVR as well as the decrement of RBF in response to the infusion of Ang II in all groups receiving vehicle or A779. Te literature has documented the dose-dependent pressor responses to Ang II [12][13][14]. Ang II, as one of the most important peptides of RAS, elicits vasoconstrictor efects mediated by AT1R [2].…”