title: Endothelin 1-induced pressor response and vasopressin release in rats with heart failure.
abstract: Heart failure (HF) is characterized by activation of both neurohumoral and sympathetic nervous systems. Specifically, HF is associated with increases in vasopressin (VP) and endothelin (ET) and in arterial baroreflex dysfunction. Hypothesis was that central ET-1 potentiates VP secretion in HF due to impaired pressor response and diminished arterial baroreflex inhibition. Male Sprague-Dawley rats were studied 42 to 54 days after sham or coronary ligation (HF) and 7 days after sinoaortic denervation (SAD). Conscious rats received intracerebroventricular artificial cerebrospinal fluid (CSF), 10 pmol of ET-1, 40 nmol BQ123, or both. Basal mean arterial pressure (MAP) did not differ, but heart rate and left ventricular end-diastolic pressure were significantly higher in HF and HF/SAD. Baseline VP was higher in both HF and HF/SAD: 5.9 +/- 0.4 pg/ml and 5.6 +/- 0.7 pg/ml versus sham 2.8 +/- 0.2 and sham-SAD 1.6 +/- 0.2 (p < 0.001). ET-1 increased MAP in sham rats by 16.0 +/- 1.4 mm Hg, but only by 7.4 +/- 2.2 mm Hg in HF (p < 0.05 versus sham) and 5.8 +/- 2.4 mm Hg in HF/SAD (p < 0.01 versus sham SAD). Tachycardic response was attenuated in HF/SAD compared with HF alone. After ET-1, VP increased by 3.3 +/- 2.7 pg/ml in sham and 13.3 +/- 2.6 pg/ml in HF (p < 0.05), but only by 2.3 +/- 0.7 pg/ml in HF/SAD (p < 0.01 versus HF). BQ123 blocked all responses to exogenous ET-1 but had no effect on baseline values. Thus, ET-evoked a lower pressor response in HF due to an impaired ability to increase heart rate and cardiac output. ET-1-induced VP release in HF was higher than in controls as a result of lower pressor response or impaired arterial baroreflex. In contrast to rats with normal left ventricular function, sinoaortic denervation in HF failed to potentiate either pressor response or VP secretion. These findings suggest that acute, though modest, increases in afterload may increase left atrial pressure more in HF/SAD such that cardiopulmonary reflexes may be activated or natriuretic peptides may be released that further restrain both pressor and VP responses.
authors.affiliation: Department of Medicine, Wayne State University School of Medicine, and John D. Dingell VA Medical Center, Detroit, Michigan, USA. nrossi@intmed.wayne.edu
authors.forename: Noreen F
authors.initials: NF
authors.lastname: Rossi
authors.forename: Haiping
authors.initials: H
authors.lastname: Chen
authors.forename: Timothy I
authors.initials: TI
authors.lastname: Musch
mesh_terms: D000818:Animals; D019332:Endothelin-1 / Q000494:pharmacology*; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D011311:Pressoreceptors / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014667:Vasopressins / Q000378:metabolism*
chemical_list: D019332:Endothelin-1; D014667:Vasopressins