Brainstem AT1R and iNOS Are Involved in Sympathoexcitation of Renovascular Hypertension

Hypertension is a major public health concern affecting ~70 million adults in the United States.1 Although essential hypertension is the most common etiology, the prevalence of atherosclerotic renovascular hypertension is rising especially in high-risk groups such as those with extrarenal atherosclerosis and heart failure.2 Activation of the renin–angiotensin system is a hallmark of renovascular hypertension. The importance of sympathetic hyperactivity has been known for some time but only recently garnered increasing attention.3 Mechanisms leading to sympathoexcitation are still not fully understood. In this issue of American Journal of Hypertension, Elizabeth Barbosa de Oliveira-Sales and her colleagues4 have effectively employed the two-kidney one-clip (2K-1C) hypertensive rat model to study the rostral ventrolateral medulla (RVLM), a brainstem locus critically involved in regulating sympathetic vasomotor tone. They measured mRNA and protein expression of AT1 receptors (AT1R) and inducible nitric oxide synthase (iNOS) in RVLM tissue from 6-week sham-clipped and 2K-1C Wistar rats. In separate sets of urethane anesthetized sham-clipped and 2K-1C rats, they assessed hemodynamic responses and renal sympathetic nerve activity (RSNA) after microinjection of losartan or the iNOS inhibitor aminoguanidine into RVLM.