The Effects of Angiotensin II and Angiotensin-(1–7) in the Rostral Ventrolateral Medulla of Rats on Stress-Induced Hypertension

Abstract

We have shown that angiotensin II (Ang II) and angiotensin-(1–7) [Ang-(1–7)] increased arterial blood pressure (BP) via glutamate release when microinjected into the rostral ventrolateral medulla (RVLM) in normotensive rats (control). In the present study, we tested the hypothesis that Ang II and Ang-(1–7) in the RVLM are differentially activated in stress-induced hypertension (SIH) by comparing the effects of microinjection of Ang II, Ang-(1–7), and their receptor antagonists on BP and amino acid release in SIH and control rats. We found that Ang II had greater pressor effect, and more excitatory (glutamate) and less inhibitory (taurine and γ-aminobutyric acid) amino acid release in SIH than in control animals. Losartan, a selective AT1 receptor (AT1R) antagonist, decreased mean BP in SIH but not in control rats. PD123319, a selective AT2 receptor (AT2R) antagonist, increased mean BP in control but not in SIH rats. However, Ang-(1–7) and its selective Mas receptor antagonist Ang779 evoked similar effects on BP and amino acid release in both SIH and control rats. Furthermore, we found that in the RVLM, AT1R, ACE protein expression (western blot) and ACE mRNA (real-time PCR) were significantly higher, whereas AT2R protein, ACE2 mRNA and protein expression were significantly lower in SIH than in control rats. Mas receptor expression was similar in the two groups. The results support our hypothesis and demonstrate that upregulation of Ang II by AT1R, not Ang-(1–7), system in the RVLM causes hypertension in SIH rats by increasing excitatory and suppressing inhibitory amino acid release.

Attenuation of angiotensin type 2 receptor function in the rostral ventrolateral medullary pressor area of the spontaneously hypertensive rat

“…It is possible that protein expression for AT 2 Rs is decreased and that for AT 1 Rs is increased in the RVLM of SHR. Such imbalance in AT 2 Rs and AT 1 Rs has been reported in the RVLM of rats with stress-induced hypertension (10). The reduction in AT 2 R expression in the RVLM of SHR is expected to result in attenuated responses to their blockade.…”

“…Most of the biological actions of ANG II are mediated via AT 1 Rs (3–5). In recent years, AT 2 Rs have also been implicated in some actions of ANG II (5–6, 9–10). Although the presence of AT 2 Rs predominates in fetal life (12), these receptors are present in adults also (2, 11).…”

Effects of angiotensin type 2 receptor on secretion of the locus coeruleus in stress-induced hypertension rats

“…Du has reported the expression of AT 2 receptor expression was significantly lower in the brain of SIH rats (Du et al, 2013). Our results also implied the attenuation of presynaptic action of brain AT 2 receptor might play a functional role in the pathophysiological mechanism of SIH in rats.…”

Vasopressin V1a receptors mediate the hypertensive effects of [Pyr1]apelin‐13 in the rat rostral ventrolateral medulla

“…), Bachem, Weil am Rhein, Germany; Ang II, 100 pmol (Du et al . ), Sigma‐Aldrich; VP, 50 pmol (Kc et al . ), Bachem, Germany; OT, 50 pmol (Mack et al .…”

“…Drug solutions were prepared in accordance with the manufacturers' instructions, diluted to the required concentration (consistent with a large body of literature on the physiological effects of drugs used in the RVLM and other brain regions) (Zhang et al 2009a, b;Huber & Schreihofer 2011;Zhang et al 2014;Du et al 2013;Seyedabadi et al 2002;Kc et al 2002;Mack et al 2002;Lu et al 2015) in normal saline and aliquots stored at −20°C. RVLM injections were made using single-barrelled micropipettes (1-5 μl calibrated microcapillary tube; Sigma-Aldrich, Poole, UK), pulled and cut to give a tip diameter of < 100 μm, connected to a manual pressure injection device.…”