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

• Published in: Clinical and experimental hypertension (1993) 2016-02, Vol.38 (2), p.209-217
• Main Authors: Kawabe, Tetsuya, Iwasa, Masamitsu, Kawabe, Kazumi, Sapru, Hreday N.
• Format: Article
• Language: English
• Subjects: Angiotensin II Type 2 Receptor Blockers - pharmacology; Animals; Arterial Pressure - drug effects; Blood pressure; Blood Pressure - drug effects; Glutamic Acid - pharmacology; Heart Rate - drug effects; Hypertension; Imidazoles - pharmacology; Immunohistochemistry; Male; Medulla Oblongata - drug effects; Medulla Oblongata - metabolism; Microinjections; Neurons - metabolism; PD123319; Pyridines - pharmacology; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Rats, Wistar; Receptor, Angiotensin, Type 2 - metabolism; Spinal Cord Lateral Horn - metabolism; Splanchnic Nerves - drug effects; sympathetic nerve activity
• ISSN: 1064-1963; 1525-6006
• DOI: 10.3109/10641963.2015.1081229

We hypothesized that blockade of angiotensin II type 2 receptors (AT 2 Rs) 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 (AT 2 R 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. AT 2 R 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 AT 2 Rs are present on the RVLM neurons projecting to the IML and their blockade results in sympathoexcitatory responses. Activation of AT 2 Rs has an inhibitory influence in the RVLM and these receptors are tonically active. Attenuation of the function of AT 2 Rs in the RVLM may play a role in genesis and/or maintenance of hypertension in SHR.