Carbon monoxide (CO) produced through the degradation of heme by hemeoxygenases (HO) regulates blood pressure both centrally and peripherally. This study by Nassar et al. was designed to elucidate the role of the HO-CO-soluble guanylyl cyclase pathway in the rostral ventrolateral medulla (RVLM) in the control of blood pressure in spontaneous hypertensive rats (SHRs). These integrative studies in conscious rats present direct evidence that locally released HO products (CO and/or biliverdin/bilirubin) in the RVLM lowers blood pressure by inhibiting presympathetic neuronal activity. Significantly higher basal RVLM HO catalytic activity, along with higher HO-1, but not HO-2, expression was observed in SHR. Selective inhibition of HO-1 also leads to increases in RVLM neuronal activity and mean arterial pressure. The HO products biliverdin/bilirubin also contribute to the greater neurochemical and cardiovascular responses elicited by HO, at least in part via activation of neuronal nitric-oxide synthase (nNOS). These findings suggest a protective role for RVLM HO-nNOS pathway and understanding the cross-talk in the HO-nNOS pathways in the RVLM. The mechanisms that modulate the antioxidant activity of RVLM HO-1 could lead to the development of novel therapeutics to treat hypertension.
See article at J Pharmacol Exp Ther 2011, 339:267–274.
- Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics