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

Abstract

We hypothesized that blockade of angiotensin II type 2 receptors (AT₂Rs) in the rostral ventrolateral medullary pressor area (RVLM) may elicit sympathoexcitatory responses which are smaller in hypertensive rats compared to normotensive rats. This hypothesis was tested in urethane-anesthetized, artificially ventilated male 14-week-old spontaneously hypertensive rats (SHR). Age-matched male Wistar–Kyoto rats (WKY) and Wistar rats were used as controls. PD123319 (AT₂R antagonist) was microinjected into the RVLM and mean arterial pressure (MAP), heart rate (HR) and greater splanchnic nerve activity (GSNA) were recorded. Increases in MAP, HR and GSNA elicited by unilateral microinjections of PD123319 into the RVLM were significantly smaller in SHR when compared with those in WKY and Wistar rats. Unilateral microinjections of l-glutamate (l-Glu) into the RVLM elicited greater increases in MAP and GSNA in SHR compared to those in WKY. AT₂R immunoreactivity was demonstrated in the RVLM neurons which were retrogradely labeled from the intermediolateral cell column (IML) of the spinal cord. These results indicate that AT₂Rs are present on the RVLM neurons projecting to the IML and their blockade results in sympathoexcitatory responses. Activation of AT₂Rs has an inhibitory influence in the RVLM and these receptors are tonically active. Attenuation of the function of AT₂Rs in the RVLM may play a role in genesis and/or maintenance of hypertension in SHR.

• Blood pressure
• hypertension
• microinjections
• PD123319
• sympathetic nerve activity

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Funding

This research was supported by NIH grants R01-HL024347 and R01-HL076248 awarded to Dr. H. N. Sapru.