Hemeoxygenase‐carbon monoxide signaling in the rostral ventrolateral medulla is implicated in ethanol‐evoked sympathoexitation and pressor response in the SHR

Abstract

Reported studies including ours have identified the rostral ventrolateral medulla (RVLM) as a major brainstem area for ethanol‐evoked sympathoexcitation, which elicits greater pressor response in spontaneously hypertensive rats (SHRs) via activation of NE‐containing neurons in the RVLM. Recent evidence supports a critical role for carbon monoxide (CO) in brainstem control of blood pressure, sympathetic activity RVLM neuronal activity. HO is the rate‐limiting enzyme responsible for the catabolism of heme into biliverdin, CO, and iron. Hence, we hypothesized a role for brainstem HO‐CO signaling in the central cardiovascular actions of ethanol. To this end, 30 male SHR and 30 male WKY rats were divided into three groups (n=10, each group for each strain) receiving (i) aCSF as control; (ii) ethanol (10ug) following either a) hemin (1nmol) or b) aACSF. Microinjection of ethanol elicited greater and longer lasting increase in mean arterial pressure (MAP) and NE (measured by in‐vivo electrochemistry) in SHRs compared than (WKY). Hemin microinjection elicited significantly greater and longer‐lasting reductions in BP and RVLM NE in SHRs. Moreover, HO activity was significantly increased and reduced in SHRs following hemin and ethanol treatment respectively. On the other hand animals receiving ethanol following hemin pretreatment exhibited attenuated HO activity compared to hemin treated rats but higher activity compared to ethanol treated animals. These findings implicate RVLM HO‐CO signaling in ethanol induced increases in RVLM presympathetic neuronal activity and blood pressure in the SHR.