Brain renin-angiotensin system dysfunction in hypertension: recent advances and perspectives.
This review focuses on the dysfunction of the intrinsic brain renin-angiotensin system (RAS) in the pathogenesis of hypertension. Hyperactivity of the brain RAS plays a critical role in mediating hypertension in both humans and animal models of hypertension, including the spontaneously hypertensive rat (SHR). The specific mechanisms by which increased brain RAS activity results in hypertension are not well understood but include increases in sympathetic vasomotor tone and impaired arterial baroreflex function. We discuss the contribution of endogenous angiotensin (Ang) II actions on presympathetic vasomotor rostral ventrolateral medulla neurons to enhance sympathetic activity and maintain hypertension. In addition, we discuss Ang II-induced attenuation of afferent baroreceptor feedback within the nucleus tractus solitarius and its relevance to the development of hypertension. We also outline the cellular and molecular mechanisms of Ang II signal transduction that may be critical for the initiation and establishment of hypertension. In particular, we present evidence for a phosphoinositide-3-kinase-dependent signaling pathway that appears to contribute to hypertension in the SHR, possibly via augmented Ang II-induced increases in neuronal firing rate and enhanced transcriptional noradrenaline neuromodulation. Finally, we outline future directions in utilizing our understanding of the brain RAS dysfunction in hypertension for the development of improved therapeutic intervention in hypertension.
Veerasingham
Shereeni J
SJ
Department of Physiology and Functional Genomics, University of Florida, USA.
Raizada
Mohan K
MK
D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D017704:Baroreflex / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000201:enzymology / Q000503:physiopathology*; D008526:Medulla Oblongata / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology; D012084:Renin-Angiotensin System / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology
D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D019869:Phosphatidylinositol 3-Kinases