[show abstract][hide abstract] ABSTRACT: Although previously thought to be synthesized solely in adrenal cortex, we have recently showed that aldosterone is also produced in and the expression of CYP11B2 mRNA was induced in the failing or hypertensive human ventricle. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are cardiac hormones with wide biological effects, including inhibition of renin and aldosterone production. We hypothesized that natriuretic peptides reduce the expression of CYP11B2 mRNA in the heart.
To test this hypothesis, we examined whether endogenous or exogenous natriuretic peptides reduce the expression of CYP11B2 mRNA using real-time reverse transcription-polymerase chain reaction. By using HS 142-1, a functional guanylyl cyclase-A type receptor antagonist, we showed that angiotensin II (AngII) pretreated with HS 142-1 increased CYP11B2 mRNA expression (1.62+/-0.12-fold, HS 142-1+AngII 10(-7) mol/L versus AngII 10(-7) mol/L alone, P<0.0001). The treatment with exogenous (10(-6) mol/L) ANP and BNP reduced CYP11B2 mRNA expression (ANP, P=0.0042; BNP, P=0.0012).
We showed that endogenous and exogenous natriuretic peptides reduced CYP11B2 mRNA expression in cultured neonatal rat cardiocytes. This may inhibit the cardiac renin-angiotensin-aldosterone system by suppressing the gene expression of CYP11B2 and restraining cardiac hypertrophy and fibrosis.
[show abstract][hide abstract] ABSTRACT: To assess the relation of hyperaldosteronism and potassium depletion to the intensity of diuretic therapy we have measured plasma aldosterone by radioimmunoassay and total exchangeable potassium by radioisotope dilution in 24 patients when they were stable at the end of their preparation for cardiac operation. Some patients required intensive frusemide therapy to reach an optimal state for operation and many showed hyperaldosteronism. Plasma aldosterone was significantly related to daily dose of frusemide (r=0.77). Depletion of total exchangeable potassium expressed in terms of predicted weight was significantly related to plasma aldosterone (r= -0.64). The reduction in total exchangeable potassium is interpreted as chiefly related to loss of lean tissue mass from the wasting that leads to cardiac cachexia, but evidence is presented on the basis of measurements of extracellular fluid volume as sulphate space (20 patients) of entry of sodium into the cells which may indicate a true cellular potassium loss. Although plasma potassium is usually easily maintained with oral potassium supplements or aldosterone antagonists, we postulate that intensive diuretic therapy in severe heart disease may provoke hyperaldosteronism which accentuates potassium loss and may contribute to wasting and to intracellular potassium depletion in critical tissue, such as myocardium.
[show abstract][hide abstract] ABSTRACT: Guanylyl cyclase-A (NPR-A; GC-A) is the major and possibly the only receptor for atrial natriuretic peptide (ANP) or B-type natriuretic peptide. Although mice deficient in GC-A display an elevated blood pressure, the resultant cardiac hypertrophy is much greater than in other mouse models of hypertension. Here we overproduce GC-A in the cardiac myocytes of wild-type or GC-A null animals. Introduction of the GC-A transgene did not alter blood pressure or heart rate as a function of genotype. Cardiac myocyte size was larger (approximately 20%) in GC-A null than in wild-type animals. However, introduction of the GC-A transgene reduced cardiac myocyte size in both wild-type and null mice. Coincident with the reduction in myocyte size, both ANP mRNA and ANP content were significantly reduced by overexpression of GC-A, and this reduction was independent of genotype. This genetic model, therefore, separates a regulation of cardiac myocyte size by blood pressure from local regulation by a GC-mediated pathway.
Proceedings of the National Academy of Sciences 03/2001; 98(5):2703-6. · 9.74 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.