Regulation of vascular tone by endothelium-derived hyperpolarizing factor.

1. Endothelium-derived hyperpolarizing factor (EDHF) mediates the nitric oxide (NO)-independent component of the relaxation in rat mesenteric arteries. The relationship between hyperpolarization and vascular tone was studied by simultaneous recording of membrane potential with intracellular microelectrodes and tension in ring segments of rat mesenteric arteries. 2. By depolarizing arteries with high potassium solutions, it was determined that the threshold for contraction is approximately -46 mV. Maximum contraction was attained when the arteries were depolarized to -20 mV. Thus, 1 mV depolarization resulted in an approximate 4% increase in tone. This relationship was not altered in spontaneously hypertensive rats. 3. Noradrenaline (0.3 mumol/L) caused contraction and depolarized arteries by 13 mV. Acetylcholine caused endothelium-dependent relaxation and hyperpolarization up to 14 mV. In the presence of N omega-nitro-L-arginine, the EDHF-mediated relaxation was correlated to hyperpolarization. A hyperpolarization of 1 mV corresponded to a 4.3% decrease of the induced tone. 4. At concentrations (10 mumol/L) causing total relaxation, the maximum hyperpolarization induced by NO was only 7.6 mV. 5. A maximum relaxation of 88% was observed with pinacidil (3 mumol/L), despite a 25 mV hyperpolarization. Relaxations to NO and pinacidil were not correlated with hyperpolarization. At similar levels of hyperpolarization, NO and pinacidil elicited more relaxation than EDHF. 6. These studies show that vascular tone is very sensitive to membrane potential change in the range between -46 and -20 mV in the rat mesenteric artery. The relaxation response to EDHF, unlike that to NO and pinacidil, can be accounted for solely by its effect on the membrane potential.

Comparison of two predictive models for prognosis in critically ill patients in a Veteran's Affairs Medical Center coronary care unit.

STUDY OBJECTIVE: The acute physiologic and chronic health evaluation score has been developed to assess prognosis in critically ill patients. Knaus et al initially determined and validated diagnosis-specific coefficients for prediction of outcome in a group of multidisciplinary ICUs. Teskey et al found different coefficients for cardiac diagnoses in a retrospective analysis of coronary care unit (CCU) only patients. This study compares the actual mortality in a Veteran's Affairs Medical Center (VAMC) CCU with the mortality predicted by the two equations. DESIGN AND SETTING: Data were prospectively collected for patients admitted to the medical CCU at a university-affiliated, tertiary care VAMC. PATIENTS: Patients (n = 338) admitted to the CCU with the diagnoses of coronary artery disease (CAD), myocardial infarction (MI), congestive heart failure (CHF), arrhythmia (Arr), and other cardiac-related diagnoses. RESULTS: The entire CCU population showed no significant differences from either the predictions by Knaus et al and Teskey et al in 1991. However, when specific disease states were analyzed as a whole, significant differences from both prediction models for CAD and MI actual mortality were found. Teskey et al was a better predictor for the Arr and CHF population, while both were equally reliable for other. CONCLUSIONS: Either prediction model is reliable for a CCU population in general. However, diagnosis-specific coefficients of Teskey et al appear to correlate better with actual mortality for this VAMC. Significant outcome differences compared with those predicted may reflect the patient population specific to a VAMC.

Modulation of Ca(2+)-activated K+ channel activity by tyrosine kinase inhibitors in vascular smooth muscle cell.

The effects of the tyrosine kinase inhibitors genistein, lavendustin A, and tyrphostin A25 on Ca(2+)-activated K+ channel activities in freshly isolated single vascular smooth muscle cells from the rat tail artery were studied by patch clamp recording technique. Genistein (5-50 microM) and lavendustin A (10 microM) increased whole-cell Ca(2+)-activated K+ channel currents. Increase in single channel activities by genistein and lavendustin A was also observed in excised inside-out patches. Diadzein (15 microM), an inactive analogue of genistein, did not alter channel activities. Tyrphostin A25 (10 nM), which had no significant effect on whole-cell currents in concentrations up to 50 microM, increased the open probability of the channels by 841% in inside-out patches. No potentiation of whole-cell and single channel activities by genistein was observed when ATP was omitted from the intracellular solutions. These observations suggest that tyrosine kinase modulates Ca(2+)-activated K+ channel activities in vascular smooth muscle cells.