veratrine and acetovanillone

Patients on a low salt (LS) diet have increased mortality.. To determine whether reduction in NO bioactivity may contribute to the LS-induced cardiac dysfunction and mortality.. Adult male mongrel dogs were placed on LS (0.05% sodium chloride) for 2 weeks. Body weight (25.4 + or - 0.4 to 23.6 + or - 0.4 kg), left ventricular systolic pressure (137.0 + or - 3.4 to 124.0 + or - 6.7 mm Hg), and mean aortic pressure (111 + or - 3.1 to 98 + or - 4.3 mm Hg) decreased. Plasma angiotensin II concentration increased (4.4 + or - 0.7 to 14.8 + or - 3.7 pg/mL). Veratrine-induced (5 microg/kg) NO-mediated vasodilation was inhibited by 44% in LS; however, the simultaneous intravenous infusion of ascorbic acid or apocynin acutely and completely reversed this inhibition. In LS heart tissues, lucigenin chemiluminescence was increased 2.3-fold to angiotensin II (10(-8) mol/L), and bradykinin (10(-4) mol/L) induced reduction of myocardial oxygen consumption in vitro was decreased (40 + or - 1.3% to 16 + or - 6.3%) and completely restored by coincubation with tiron, tempol or apocynin. Switching of substrate uptake from free fatty acid to glucose by the heart was observed (free fatty acid: 8.97 + or - 1.39 to 4.53 + or - 1.12 micromol/min; glucose: 1.31 + or - 0.52 to 6.86 + or - 1.78 micromol/min). Western blotting indicated an increase in both p47(phox) (121%) and gp91(phox) (44%) as did RNA microarray analysis (433 genes changed) showed an increase in p47(phox) (1.6-fold) and gp91(phox) (2.0 fold) in the LS heart tissue.. LS diet induces the activation of the renin-angiotensin system, which increases oxidative stress via the NADPH oxidase and attenuates NO bioavailability in the heart.

Topics: Acetophenones; Angiotensin II; Animals; Ascorbic Acid; Coronary Vessels; Diet, Sodium-Restricted; Dogs; Fatty Acids; Gene Expression Profiling; Glucose; Hemodynamics; Infusions, Intravenous; Lactates; Male; Myocardium; NADPH Oxidases; Nitric Oxide; Oligonucleotide Array Sequence Analysis; Oxidative Stress; Oxygen Consumption; Renin-Angiotensin System; Superoxides; Vasodilation; Veratrine; Weight Loss

Few studies have examined the effect of acute pressure overload on endothelial function in the coronary microcirculation.. In instrumented conscious dogs with heart rate held constant, veratrine caused a cholinergic nitric oxide (NO)-dependent increase in coronary blood flow by 23+/-3 mL/min (Bezold-Jarisch reflex). Ten minutes after release of constriction of the ascending aorta to increase left ventricular (LV) systolic pressure to 214+/-5 mm Hg for 30 minutes, the veratrine-induced increase in coronary blood flow (7+/-1 mL/min) was reduced by 66% and remained depressed for 2 hours (ie, endothelial stunning [ES]). Nitrite production from isolated coronary microvessels during ES was not different from normal. Ascorbic acid (AA), losartan, or apocynin prevented ES. Myocardial oxygen consumption (MVO2) of LV tissue was measured in vitro in response to bradykinin with preincubation of angiotensin II for 30 minutes. Bradykinin (10(-4) mol/L)-induced reduction in MVO2 was reversed in a concentration-dependent manner by angiotensin II (38+/-1% versus 19+/-2% at 10(-8) mol/L) and restored by coincubation of AA (37+/-2%), tempol (33+/-2%), losartan (34+/-2%), or apocynin (36+/-1%). Exogenous NO-induced reduction in MVO2 was not altered by angiotensin II. Angiotensin II increased lucigenin-detectable superoxide anion in LV tissue in a manner that was inhibited by bradykinin, AA, tempol, losartan, or apocynin.. Endothelial stunning is caused by oxidant processes inhibited by ascorbate, and the activation of NAD(P)H oxidase by increased angiotensin II plays an important role in this process.

Topics: Acetophenones; Angiotensin II; Animals; Ascorbic Acid; Bradycardia; Bradykinin; Coronary Circulation; Cyclic N-Oxides; Dogs; Hypotension; Ligation; Losartan; Myocardial Stunning; Nitric Oxide; Oxidative Stress; Pressure; Reflex; Spin Labels; Superoxides; Veratrine