Role of endothelin receptor subtypes in volume-stimulated ANF secretion.

The role of endothelin (ET) receptors was tested in volume-stimulated atrial natriuretic factor (ANF) secretion in conscious rats. Mean ANF responses to slow infusions (3 x 3.3 ml/8 min) were dose dependently reduced (P < 0.05) by bosentan (nonselective ET-receptor antagonist) from 64.1 +/- 18.1 (SE) pg/ml (control) to 52.6 +/- 16.1 (0.033 mg bosentan/rat), 16.1 +/- 7.6 (0. 33 mg/rat), and 11.6 +/- 6.5 pg/ml (3.3 mg/rat). The ET-A-receptor antagonist BQ-123 (1 mg/rat) had no effect relative to DMSO controls, whereas the putative ET-B antagonist IRL-1038 (0.1 mg/rat) abolished the response. In a second protocol, BQ-123 (>/=0.5 mg/rat) nonsignificantly reduced the peak ANF response (106.1 +/- 23.0 pg/ml) to 74.0 +/- 20.5 pg/ml for slow infusions (3.5 ml/8.5 min) but reduced the peak response (425.3 +/- 58.1 pg/ml) for fast infusions (6.6 ml/1 min) by 49.9% (P < 0.001) and for 340 pmoles ET-1 (328.8 +/- 69.5 pg/ml) by 83.5% (P < 0.0001). BQ-123 abolished the ET-1-induced increase in arterial pressure (21.8 +/- 5.2 mmHg at 1 min). Changes in central venous pressure were similar for DMSO and BQ-123 (slow: 0.91 and 1.14 mmHg; fast: 4.50 and 4.13 mmHg). The results suggest 1) ET-B receptors mainly mediate the ANF secretion to slow volume expansions of <1.6%/min; and 2) ET-A receptors mainly mediate the ANF response to acute volume overloads

C-type natriuretic peptide levels in cor pulmonale and in congestive heart failure.

BACKGROUND--C-type natriuretic peptide (CNP) is a recent addition to the family of natriuretic peptides which includes atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). Whilst the levels of ANP and BNP are increased in conditions such as congestive heart failure and cor pulmonale, abnormal levels of CNP in these conditions have not been reported. METHODS--Plasma levels of CNP were measured by specific radioimmunoassay in 12 young normal controls, 12 elderly normal controls, 12 patients with NYHA grade III-IV congestive heart failure, and in 16 patients with hypoxaemic cor pulmonale. RESULTS--Mean (SE) plasma levels of CNP were similar in young normal controls (0.46(0.03) pmol/l), elderly normal controls (0.43(0.05) pmol/l), and in patients with congestive heart failure (0.33(0.2) pmol/l). In patients with cor pulmonale, however, plasma levels of CNP were raised (1.39(0.27) pmol/l) 3.2-fold compared with age-matched controls. CONCLUSIONS--In cor pulmonale the increased plasma levels of CNP were not as great as the previously observed increases in levels of ANP (5.6-fold) or BNP (18.5-fold) in comparable patients. CNP may therefore be less important than ANP or BNP as a circulating counter-regulatory peptide in conditions of overactivity of the renin angiotensin system