IntroductionUsing a specific radioimmunoassay for human brain natriuretic peptide (hBNP) with a monoclonal antibody, we have investigated its synthesis, secretion, and clearance in comparison with those of atrial natriuretic peptide (ANP) in normal subjects and patients with congestive heart failure (CHF Since the discovery of atrial natriuretic peptide (ANP)' in the heart (1-5) and subsequently in the brain (5-10), ANP has been implicated in body fluid homeostasis and blood pressure control as a hormone and as a neuropeptide ( 1-1 1). We and others have previously demonstrated that the synthesis and secretion of ANP in the heart are increased in patients with congestive heart failure (CHF) in relation to its severity (12-18).More recently, brain natriuretic peptide (BNP) was isolated from the porcine brain (19), which has either 26 or 32 amino acid residues, porcine (p) respectively (20), with a remarkable sequence homology to ANP and has peripheral and central actions similar to those of ANP (19,(21)(22)(23). BNP is also synthesized in, and secreted into the circulation from, the porcine heart (24, 25). Subsequently, we and others isolated rat BNP (rBNP) with 45 amino acid residues from the rat heart (26-28). To date, however, the information on BNP in humans is scarce, mainly for lack ofcross-reactivity of human BNP (hBNP) with antisera against pBNP or rBNP.Recently

We injected acetylcholine (ACh), the neurotransmitter of the parasympathetic nervous system, into the coronary arteries of 28 patients with variant angina. Injection of 10 to 80 gg ACh into the coronary artery responsible for the attack induced spasm together with chest pain and ST segment elevation or depression on the electrocardiogram in 30 of the 32 arteries of 25 of the 27 patients. The injection of 20 to 100 gg ACh into the coronary artery not responsible for the attack in 18 patients resulted in various degrees of constriction in most of them, but no spasm in any of them. After intravenous injection of 1.0 to 1.5 mg atropine sulfate, the injection of ACh into the coronary artery responsible for the attack did not induce spasm or attack in any of the nine coronary arteries injected in eight patients. We conclude that the intracoronary injection of ACh induces coronary spasm and attack in patients with variant angina and that the activity of the parasympathetic nervous system may play a role in the pathogenesis of coronary spasm. We also conclude that the intracoronary injection of ACh is a useful test for provocation of coronary spasm. Circulation 74, No. 5, 955-963, 1986. IT IS NOW widely accepted that spasm of an epicardial coronary artery (coronary spasm) plays an important role in the pathogenesis, not only of variant angina, but also of other forms of resting angina, some types of exertional angina, and types of acute myocardial infarction. quently Endo et al.'0 confirmed our results. On the basis of this fact and the fact that the activity of the parasympathetic nervous system is enhanced at rest and is suppressed by physical activity," we postulated that the activity of parasympathetic nervous system might be related to the pathogenesis of variant angina or coronary spasm.7 It has been shown that stimulation of the parasympathetic (vagus) nerve or intracoronary injection of ACh causes coronary vasodilatation, as demonstrated by an increase in coronary blood flow in dogs,'2-'5 and that ACh dilates isolated epicardial coronary arteries in dogs'6 and monkeys. 17 In humans subcutaneous injection of methacholine causes profound dilatation of systemic vasculature, resulting in a transient fall in blood pressure and compensatory tachycardia due to reflex sympathetic discharge.7 We therefore speculated that coronary spasm might be induced by sympathetic discharge by way of a-adrenergic stimulation.7 Recently, however, reports have appeared that show that ACh contracts strips of human coronary arteries obtained from hearts of transplant recipients'8 or cadav-955

Synthetic a-human atrial natriuretic polypeptide was infused in patients with congestive heart failure (CHF) (New York Heart Association class III or IV) and in those without CHF. The infusion of atrial natriuretic polypeptide (ANP) at a rate of 0. 1 gg/kg/min significantly decreased pulmonary capillary wedge pressure and increased stroke volume index in all of the patients with CHF, whereas it decreased pulmonary capillary wedge pressure but caused no significant change in stroke volume index in the patients without CHF. Concomitant significant reductions in total systemic resistance were observed in both groups of patients. The ANP infusion significantly increased the urine volume, the excretion of sodium, and endogenous creatinine clearance in the patients without CHF. In the patients with CHF, it also showed a tendency to increase all these variables, but the urine volume did not correlate with the reduction in pulmonary capillary wedge pressure. The ANP infusion also decreased plasma aldosterone concentrations in these patients, although no significant difference was observed in the decrement of the plasma aldosterone concentration in the patients with and those without CHF. These findings indicate that the ANP infusion improves left ventricular function in patients with CHF, and suggest that this improvement results mainly from the vasodilating activity of ANP.Circulation 76, No. 1, 115-124, 1987. AFTER THE EPOCHAL discovery of the potent diuretic, natriuretic, and vasorelaxant activities in an extract from rat atria by de Bold et al. ,' multiple forms of natriuretic polypeptides with high and low molecular weights have been isolated fromn rat and human atria and implicated in the control of blood pressure, water, and electrolyte balance.2-1 Accumulating evidence indicates that a-atrial natriuretic polypeptide (a-ANP)

Highly active NiFeO electrocatalysts for the oxygen evolution reaction (OER) suffer gradual deactivation with time owing to the loss of Fe species from the active sites into solution during catalysis. The anodic deposition of a CeO layer prevents the loss of such Fe species from the OER catalysts, achieving a highly stable performance. The CeO layer does not affect the OER activity of the catalyst underneath but exhibits unique permselectivity, allowing the permeation of OH and O through while preventing the diffusion of redox ions through the layer to function as a selective O -evolving electrode. The use of such a permselective protective layer provides a new strategy for improving the durability of electrocatalysts.

IntroductionTo elucidate the expression of the atrial natriuretic polypeptide (ANP) gene in the ventricle of the human failing heart, we have measured ANP and ANP messenger RNA (ANPmRNA) levels in left ventricular aneurysm obtained at operation, biopsy specimens of left ventricles from dilated cardiomyopathy (DCM) and autopsy samples of old myocardial infarction (OMI) and DCM hearts, and compared the levels with those in the normal ventricle. The ANP level (mean±SE) was 17.5±6.9 ng/g in the normal ventricle, and increased to 6603±122.2 ng/g in the left ventricular aneurysm tissues and to 3,138.6±1,642.1 ng/g in the biopsy specimens of the DCM ventricle. These levels were 40 and 200 times higher than in the normal ventricle. The increase of ANP levels was observed in both infarcted and noninfarcted regions of the OMI heart, and in the entire ventricle of the DCM heart. A significant positive correlation was found between the ANP level in aneurysm tissues and pulmonary capillary wedge pressure (r = 0.85). The ANPmRNA level in the left ventricular aneurysm showed about a 10-fold increase compared with that in the normal heart and reached 23% of that in the atrium of the same heart. A similar increase in the ANPmRNA level was observed in the entire ventricle of DCM. These data clearly indicate that the expression of the ANP gene in the ventricle is augmented in the failing heart in accordance with the severity of heart failure. In the atrium of the failing heart, ANP and ANPmRNA levels were only two times higher than those in the normal atrium. Thus, the augmentation in the expression of the ANP gene was more prominent in the ventricle than in the atrium. Taking tissue weight into account, the total content of ANPmRNA in the ventricle of the failing heart is much the same as that in the normal atrium. The ratio of the ANP level to the ANPmRNA level in the ventricle is much smaller than that in the atrium. These results suggest more rapid secretion of ANP after synthesis in the ventricle. These findings demonstrate that the expression of the ANP gene is augmented in the human ventricle of the failing heart and suggest that the ventricle becomes a substantial source of circulating ANP in congestive heart failure.Address reprint requests to Dr.