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(8) 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.
Wang
S Y
SY
Division of Cardiothoracic Surgery, Beth Israel-Deaconess Medical Center, Boston, Massachusetts, USA.
Cameron
E M
EM
Fink
M P
MP
Sellke
F W
FW
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000503:physiopathology; D016470:Bacteremia / Q000503:physiopathology*; D002908:Chronic Disease; D003326:Coronary Circulation / Q000187:drug effects; D006439:Hemodynamics; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D011942:Receptors, Adrenergic, alpha; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents