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.
Highlights
A moden life style with fast pace can cause emotional and psychological stress, which may lead to a gradual increase in hypertension in young adults
We found that Systolic blood pressure (SBP) and AT1 receptor (AT1R) protein expression in the stressed rats increased in a time-dependent manner (Fig. 1A, B)
Changes in SBP, heart rate (HR) and protein expression of AT1R became significant on the 5th day (P,0.05) (Fig. 1A, B, Table 1)
Summary
A moden life style with fast pace can cause emotional and psychological stress, which may lead to a gradual increase in hypertension in young adults. There is compelling evidence that the renin-angiotensin system (RAS) in the brain plays a vital role in regulation of arterial blood pressure (BP) and sympathetic nerve activity. Development of strategies to regulate RAS activity in the pathophysiology of hypertension is of great interest [1]. The protease renin catalyzes angiotensinogen into an inactive decameric peptide, angiotensin I (Ang I), which is converted to active octapeptide angiotensin II (Ang II) by angiotensinconverting enzyme (ACE). By binding to AT1R, Ang II desensitizates baroreflex and increases sympathetic outflow, BP and vasopressin release [2]. The role of AT2R in central regulation of BP is not clear. Angiotensin-converting enzyme homolog (ACE2) is a new component of the RAS [3,4]. ACE2 cleaves Ang I to Ang-(1–9) [4], which can be further converted into the heptapeptide Ang-(1–
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call