Subtype specific regulation of human vascular alpha(1)-adrenergic receptors by vessel bed and age.

BACKGROUND: alpha(1)-adrenergic receptors (alpha(1)ARs) regulate blood pressure, regional vascular resistance, and venous capacitance; the exact subtype (alpha(1a), alpha(1b), alpha(1 d)) mediating these effects is unknown and varies with species studied. In order to understand mechanisms underlying cardiovascular responses to acute stress and chronic catecholamine exposure (as seen with aging), we tested two hypotheses: (1) human alpha(1)AR subtype expression differs with vascular bed, and (2) age influences human vascular alpha(1)AR subtype expression. METHODS AND RESULTS: Five hundred vessels from 384 patients were examined for alpha(1)AR subtype distribution at mRNA and protein levels (RNase protection assays, ligand binding, contraction assays). Overall vessel alpha(1)AR density is 16+/-2.3fmol/mg total protein. alpha(1a)AR predominates in arteries at mRNA (P<0.001) and protein (P<0.05) levels; all 3 subtypes are present in veins. Furthermore, alpha(1)AR mRNA subtype expression varies with vessel bed (alpha(1a) higher in splanchnic versus central arteries, P<0.05); competition analysis (selected vessels) and functional assays demonstrate alpha(1a) and alpha(1b)-mediated mammary artery contraction. Overall alpha(1)AR expression doubles with age (<55 versus > or = 65 years) in mammary artery (no change in saphenous vein), accompanied by increased alpha(1b)>alpha(1a) expression (P< = 0.001). CONCLUSIONS: Human vascular alpha(1)AR subtype distribution differs from animal models, varies with vessel bed, correlates with contraction in mammary artery, and is modulated by aging. These findings provide potential novel targets for therapeutic intervention in many clinical settings.

Cardiovascular effects of intravenous triiodothyronine in patients undergoing coronary artery bypass graft surgery. A randomized, double-blind, placebo- controlled trial. Duke T3 study group.

OBJECTIVE: To test the hypothesis that triiodothyronine (T(3)) administration improves hemodynamic variables and decreases inotropic drug requirements in cardiac surgery patients. DESIGN: Prospective, randomized, double-blind, placebo-controlled trial. SETTING: Tertiary care medical center. PATIENTS: A total of 211 patients undergoing coronary artery surgery at high risk for requiring inotropic drug support. INTERVENTION: At release of aortic cross-clamp, patients were randomized to an intravenous infusion of T(3) (0.8 microg/kg followed by 0.12 microg.kg(-1).h(-1) for 6 hours), dopamine (positive control, 5 microg.kg(-1).min(-1) for 6 hours) or placebo. MAIN OUTCOME MEASURES: Perioperative hemodynamic variables, inotropic support requirements, and serum T(3) concentrations. RESULTS: Mean+/-SEM free T(3) serum concentrations decreased significantly during cardiopulmonary bypass in all groups (from 0.0035+/-0.0001 nmol/L [0.23+/-0.01 ng/dL] to 0.001+/-0.0001 nmol/L [0.7+/- 0.00 ng/dL]; P=.001) and increased to 0.0133+/-0.0004 nmol/L [0.87+/-0.03 ng/dL] (twice normal range; P<.001) following initiation of intravenous T(3). Intravenous T(3) did not change hemodynamic variables or inotropic drug requirements; however, heart rate increased (P<.001), and a trend toward decreased use of inotropic agents was demonstrated in the dopamine group. CONCLUSIONS: Triiodothyronine administration prevents decreases in serum thyroid hormone concentrations associated with cardiopulmonary bypass. Intravenous T(3) does not have dramatic effects on hemodynamic variables in this setting as has been previously suggested. Although mild effects on myocardial performance may exist, we cannot recommend at this time the routine use of intravenous T(3) as an inotropic agent in patients undergoing coronary artery bypass graft surgery.