Enhanced heme oxygenase‐CO signaling in the rostral ventrolateral medulla of SHR

Abstract

Heme oxygenase (HO)‐derived carbon monoxide (CO) is implicated in central control of blood pressure and baroreflex sensitivity. In the few reported studies that pharmacologically evaluated the activity of brainstem HO‐CO pathway, hemin was microinjected into the nucleus tractus solitarius of anesthetized normotensive rats. Whether HO‐CO signaling is upregulated (as defense mechanism) or downregulated (underlying factor for hypertension) in the rostral ventrolateral medulla of the SHR is not known. Therefore, we investigated in conscious SHRs, and their normotensive controls (WKY), the consequences of CO generation within the rostral ventrolateral medulla (RVLM) on BP, and neuronal norepinephrine (index of sympathetic activity). Hemin (1nmol) was microinjected into the RVLM and in vivo electrochemistry was used for measurement of NE changes as in our studies ( J Cardiovasc Pharmacol 45, 1‐11). Hemin microinjection elicited significantly (P<0.05) greater reductions in BP and NE in SHRs than in WKY rats; the durations of these responses were also greater in SHRs. The findings suggest exaggerated HO‐CO signaling in the RVLM of SHR, a brainstem area that controls sympathetic outflow. Such enhancement of HO‐CO signaling seems to serve as a defense mechanism to oppose further increases in BP in the SHR. The HO isoform (HO‐1 or HO‐2) implicated in these neurobiological effects remains to be elucidated.