Chronic septicemia alters alpha-adrenergic mechanisms in the coronary circulation

The purpose of the present study was to determine the effect of chronic sepsis on alpha-adrenergic responsiveness in the coronary microcirculation. Male Sprague-Dawley rats (n = 6) were made septic by intraperitoneal implantation of a gelatin capsule containing 35 mg sterile rat feces and 1 x 10(6) viable colony-forming units of Escherichia coli (strain Sm 018). Control rats (n = 6) were implanted with capsules containing only sterile feces, Forty-eight hours after surgery, subepicardial coronary arterioles (80-170 mm) were isolated. In vitro arteriolar responses were studied in a pressurized, no-flow state with video-microscopy. Chronic sepsis decreased the contractile responses to the alpha(1)-adrenoceptor agonist phenylephrine and the protein kinase C (PKC) activator 12-deoxyphorbol 13-isobutyrate 20-acetate. Relaxation responses to the alpha(2)-adrenoceptor agonist clonidine, the endothelium-dependent vasodilator adenosine 5'-diphosphate, and the PKC inhibitor staurosporine were reduced, but the relaxation to the endothelium-independent cyclic GMP-mediated vasodilator sodium nitroprusside was preserved. Relaxation to clonidine was inhibited by endothelial denudation or after blockade of nitric oxide synthase. Chronic sepsis may reduce alpha(2)-adrenoceptor-mediated relaxation of coronary microvessels by causing endothelial dysfunction. The alpha(1)-adrenergic mechanism is downregulated, possibly due to alterations in the receptor and/or downstream signal transduction via PKC. (C) 1997 Academic Press.