natriuretic-peptide--c-type and Cardiac-Output--Low

Topics: Aldosterone; Angiotensin II; Animals; Atrial Natriuretic Factor; Cardiac Output, Low; Central Nervous System; Dogs; Humans; Hypertension; Male; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Nerve Tissue Proteins; Proteins; Rats; Renin; Renin-Angiotensin System; Sheep

C-type natriuretic peptide (CNP) is a newly identified peptide that is structurally related to atrial natriuretic peptide (ANP). Although it has been suggested that CNP is released from the endothelium for the regulation of local vascular tone, no data are available concerning the vasodilatory response to CNP in humans.. Strain-gauge plethysmography was used to determine the vasodilatory effects of intra-arterially infused CNP compared with the effects of ANP infusion in 11 patients with chronic heart failure (CHF) and 11 age-matched healthy controls. Graded doses of CNP and ANP (8, 16, 32, and 48 pmol.min-1.dL-1 tissue volume) were administered randomly into the nondominant brachial artery, and forearm blood flow (FBF) was measured. No significant changes in systemic blood pressure and heart rate were found during the study. Both the absolute and percent FBF responses to ANP relative to the baseline value were significantly lower in CHF patients than in healthy controls (P < .01), whereas the responses to CNP were similar. The calculated forearm spillover of cyclic GMP (cGMP) was significantly lower in CHF patients receiving the highest dose of ANP (P < .02), whereas changes in cGMP spillover after the equimolar dose of CNP were significantly higher (P < .02), despite the lesser potency of CNP.. In patients with CHF the peripheral vasodilatory effect of ANP is attenuated, but CNP-induced peripheral vasorelaxation is preserved, with CNP being less potent for equimolar doses.

Topics: Atrial Natriuretic Factor; Blood Vessels; Cardiac Output, Low; Chronic Disease; Cyclic GMP; Female; Forearm; Humans; Injections, Intra-Arterial; Male; Middle Aged; Natriuretic Peptide, C-Type; Plethysmography; Proteins; Regional Blood Flow; Vascular Resistance; Vasodilation

The effects on myocardial function and loading conditions of clinically relevant doses of the natriuretic peptides (NP) have not been established. The actions of single doses (100 ng x kg(-1) x min(-1) iv over 30 min) of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) were studied in conscious normal dogs and in dogs with pacing-induced heart failure. All three NP reduced end-diastolic pressure in normal dogs, and ANP and BNP reduced end-diastolic volume. In heart failure ANP and BNP reduced EDP, and ANP reduced EDV. Arterial elastance was unchanged in normal dogs and in dogs with heart failure. ANP increased end-systolic elastance (E(es)) in normal dogs, whereas BNP tended to increase E(es) (P = 0.06). In dogs with heart failure, no inotropic effect was seen. In normal dogs, all NP reduced the time constant of isovolumic relaxation (tau), and ANP and BNP reduced tau in dogs with heart failure. Increases in plasma cGMP in dogs with heart failure were blunted. The NP reduced preload and enhanced systolic and diastolic function in normal dogs. Effects of ANP and BNP on preload and diastolic function were maintained in heart failure. Lack of negative inotropic effects in heart failure supports the validity of the NP as therapeutic agents.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Cardiac Output, Low; Cyclic GMP; Diastole; Dogs; Heart; Male; Myocardial Contraction; Myocardium; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Reference Values

Brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) are novel natriuretic peptides, originally isolated from porcine brain. Similar to atrial natriuretic peptide (ANP), BNP is also synthesized in and secreted from cardiocytes, but CNP is not expressed at significant levels in normal adult myocardium. Previous studies have indicated that the serum level and ventricular expression of the ANP gene were augmented in patients with heart failure. Recently, the serum level of BNP was also reported to increase in human heart failure. To examine whether or not the expression of these natriuretic peptides is regulated in ventricular myocardium in a concordant manner, we performed Northern blot analysis using total cellular RNA isolated from the diseased left ventricles of 30 cardiac transplant recipients with end-stage heart failure, seven ventricles from organ donors (control group), and two ventricles of artificially aborted 17- and 19-week-old fetuses. The levels of mRNAs encoding both BNP and ANP increased significantly (p less than 0.01) in the left ventricular myocardium from the patients with end-stage heart failure as compared with the control group. The levels of BNP mRNA correlated positively with those of ANP mRNA (r = 0.73, p less than 0.01) and negatively with those of sarcoplasmic reticulum Ca(2+)-ATPase mRNA (r = -0.66, p less than 0.01) in the left ventricular myocardium from the patients with heart failure. There was also a negative correlation between the levels of ANP and the sarcoplasmic reticulum Ca(2+)-ATPase mRNAs (r = -0.65, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Atrial Natriuretic Factor; Calcium-Transporting ATPases; Cardiac Output, Low; Female; Fetus; Gene Expression; Heart; Heart Ventricles; Humans; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Nerve Tissue Proteins; RNA, Messenger