Patient with Complicated Aortic Deformities in Association with An Atrial Septal Defect and Infective Endocarditis

Abstract

Carbon monoxide (CO) is endogenously produced from the degradation of heme, in a reaction that is catalyzed by heme oxygenase (HO). Systemic blockade of HO acutely decreases neural HO activity, and this increases arterial pressure in a manner that is reversed by CO microinjections into the nucleus tractus solitarii (NTS) of the brain stem; such findings are the original evidence that endogenous CO in the NTS serves as a tonic vasodepressor. Whilst the NTS coordinates the balance and distribution of sympathetic and parasympathetic influences on the cardiovascular system, the actions of the endogenous CO on these autonomic components have not been explored. The purpose of the current study was to identify the sympathetic and parasympathetic influences that contribute to the vasoregulatory actions of the endogenous CO system. Towards this end, male Sprague-Dawley rats were fitted with chronic femoral catheters and permitted four days recovery before conducting awake experiments. The acute blood pressure effects of an HO inhibitor, zinc deuteroporphyrin 2,4-bisglycol (ZnDPBG), were examined in animals pretreated with atropine, prazosine or propranolol to block the muscarinic, ␣1or ␤-adrenergic receptors, respectively. Administration of ZnDPBG (45 µmol/kg, IP) increased arterial pressure from 123 Ϯ 2 to 133 Ϯ 3 mm Hg (p < .05) but did not affect heart rate. The actions of ZnDPBG were not affected by pretreatment with atropine (50 mg/kg, IP) but were abolished by pretreatment with prazosine (5 mg/kg, IP). In addition, pretreatment with a beta-blocker, propranolol (15 mg/kg, IP), resulted in an abbreviated pressor response to ZnDPBG. Immunohistochemical staining and Western blot analysis confirmed that HO is present in both the NTS and adrenal medulla, but complementary experiments revealed that ZnDPBG treatment did not affect circulating levels of epinephrine. This study shows that HO is present in NTS and that the actions of ZnDPBG are independent of parasympathetic changes. While HO is present in the adrenal medulla and the pressor effect of ZnDPBG apparently arises from enhanced sympathetic tone, the HO inhibitor does not increase plasma levels of epinephrine. These findings suggest that inhibition of heme-derived CO in the NTS leads to activation of peripheral sympathetic neurons and that the consequent pressor effect arises from ␣1-adrenergic-mediated vasoconstriction and ␤1-adrenergic-mediated increases in cardiac performance.