NAD(P)H oxidase plays an important role in hypertension and its complication in aldosterone-salt rat. We questioned whether NAD(P)H oxidase subunit expression and activity are modulated by aldosterone and whether this is associated with target- organ damage. Rats were infused with aldosterone (0.75 microgram/hr/day) for 6 weeks and were given 0.9% NaCl+/-losartan (30 mg/kg/day), spironolactone (200 mg/kg/ day), and apocynin (1.5 mM/L). Aldosterone-salt hypertension was prevented completely by spironolactone and modestly by losartan and apocynin. Aldosterone increased aortic NAD(P)H oxidase activity by 34% and spironolactone and losartan inhibited the activity. Aortic expression of the subunits p47(phox), gp91(phox), and p22(phox) increased in aldosterone-infused rats by 5.5, 4.7, and 3.2-fold, respectively, which was decreased completely by spironolactone and partially by losartan and apocynin. Therefore, the increased expression of NAD(P)H oxidase may contribute to cardiovascular damage in aldosterone-salt hypertension through the increased expression of each subunit.
Acetophenones/administration & dosage ; Aldosterone/administration & dosage/*toxicity ; Aldosterone Antagonists/administration & dosage ; Angiotensin II Type 1 Receptor Blockers/administration & dosage ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/administration & dosage ; Aorta/metabolism/pathology ; Blood Pressure/drug effects ; Hypertension/chemically induced/drug therapy/*enzymology ; Kidney/metabolism/pathology ; Losartan/administration & dosage ; Male ; NADPH Oxidase/antagonists & inhibitors/*metabolism ; Organ Size ; Oxidative Stress ; Protein Subunits/metabolism ; RNA, Messenger/metabolism ; Rats ; Rats, Sprague-Dawley ; Sodium Chloride/administration & dosage ; Spironolactone/administration & dosage ; Superoxides/metabolism

To determine the role of catecholamines in regulation of potassium homeostasis, we measured the serum potassium level of 60 healthy subjects on admission and just before the induction of anesthesia, with or without propranolol administration. Catecholamine-induced hypokalemia is developed by beta-2 receptor stimulation, not mediated by insulin, renin, or aldosterone. The activation of beta-2 adrenoreceptors causes a dose-dependent decrease in plasma potassium, probably by shifting potassium into the cell. By this mechanism, epinephrine may cause hypokalemia and leads to cardiac arrhythmias. These preventive mechanism of hypokalemia may contribute to the cardioprotective action of non-selective beta adrenergic blockers. In each patient, serum potassium was measured on admission and just before induction, and a ECG was analyzed prior to surgery and lead II monitoring continued during anesthesia. Mean arterial pressure and heart rate were measured on admission, preinduction, preintubation, and preoperation. Sixty patients divided into two groups. In group I (n=30), placebo was given; Group II (n=30), 40 mg of propranolol was given orally three hours prior to the induction of anesthesia. The results are as followed; 1) Comparing the preinduction potassium level with that measured two days before operation, 33% of the control group were normokalemic(> or =3.6mEq/L), 57% hypokalemic(3.1-3.5 mEq/ L), and 10% severe hypokalemic(< or =3.0 mEq/L). In the group pretreated with propranolol, 90 were normokalemic, and 10% hypokalemic. 2) Mean serum potassium level on admission and just before induction were 3.94+/-0.31 mEq/L and 3.40+/-0.38 mEq/L, respectively, in control group; 3.99+/-0,46 mEq/L and 4.16+/-0.05 mEq/L in propranolol administered group, indicating a significant increase(P< 0.01). 3) After propranolol administration, mean arterial pressure decreased significantly before operation (P<0.05), and heart rate also decreased significantly before endotracheal intubation (P< 0.01) and before operation (P< 0.05) compared with control group. 4) No arrhythmia occurred at any time in both group of patients who noted to be hypokalemic priorly. This study suggests that the oral administration of 40 mg of propranolol may prevent hypokalemia and attenuate the rate of increase in blood pressure and heart rate after induction of anesthesia. But further studies may be necessary for more detailed mechanism in preventing hypokalemia and hemodynamic evaluations regarding propranolol.
Administration, Oral ; Adrenergic beta-Antagonists ; Aldosterone ; Anesthesia* ; Arrhythmias, Cardiac ; Arterial Pressure ; Blood Pressure ; Catecholamines ; Electrocardiography ; Epinephrine ; Heart Rate ; Hemodynamics ; Homeostasis ; Humans ; Hypokalemia* ; Insulin ; Intubation, Intratracheal ; Ions ; Plasma ; Potassium ; Propranolol* ; Renin

To determine the role of catecholamines in regulation of potassium homeostasis, we measured the serum potassium level of 60 healthy subjects on admission and just before the induction of anesthesia, with or without propranolol administration. Catecholamine-induced hypokalemia is developed by beta-2 receptor stimulation, not mediated by insulin, renin, or aldosterone. The activation of beta-2 adrenoreceptors causes a dose-dependent decrease in plasma potassium, probably by shifting potassium into the cell. By this mechanism, epinephrine may cause hypokalemia and leads to cardiac arrhythmias. These preventive mechanism of hypokalemia may contribute to the cardioprotective action of non-selective beta adrenergic blockers. In each patient, serum potassium was measured on admission and just before induction, and a ECG was analyzed prior to surgery and lead II monitoring continued during anesthesia. Mean arterial pressure and heart rate were measured on admission, preinduction, preintubation, and preoperation. Sixty patients divided into two groups. In group I (n=30), placebo was given; Group II (n=30), 40 mg of propranolol was given orally three hours prior to the induction of anesthesia. The results are as followed; 1) Comparing the preinduction potassium level with that measured two days before operation, 33% of the control group were normokalemic(> or =3.6mEq/L), 57% hypokalemic(3.1-3.5 mEq/ L), and 10% severe hypokalemic(< or =3.0 mEq/L). In the group pretreated with propranolol, 90 were normokalemic, and 10% hypokalemic. 2) Mean serum potassium level on admission and just before induction were 3.94+/-0.31 mEq/L and 3.40+/-0.38 mEq/L, respectively, in control group; 3.99+/-0,46 mEq/L and 4.16+/-0.05 mEq/L in propranolol administered group, indicating a significant increase(P< 0.01). 3) After propranolol administration, mean arterial pressure decreased significantly before operation (P<0.05), and heart rate also decreased significantly before endotracheal intubation (P< 0.01) and before operation (P< 0.05) compared with control group. 4) No arrhythmia occurred at any time in both group of patients who noted to be hypokalemic priorly. This study suggests that the oral administration of 40 mg of propranolol may prevent hypokalemia and attenuate the rate of increase in blood pressure and heart rate after induction of anesthesia. But further studies may be necessary for more detailed mechanism in preventing hypokalemia and hemodynamic evaluations regarding propranolol.
Administration, Oral ; Adrenergic beta-Antagonists ; Aldosterone ; Anesthesia* ; Arrhythmias, Cardiac ; Arterial Pressure ; Blood Pressure ; Catecholamines ; Electrocardiography ; Epinephrine ; Heart Rate ; Hemodynamics ; Homeostasis ; Humans ; Hypokalemia* ; Insulin ; Intubation, Intratracheal ; Ions ; Plasma ; Potassium ; Propranolol* ; Renin