title: Abnormal baroreflex function is dissociated from central angiotensin II receptor expression in chronic heart failure.
abstract: Neurohumoral disturbances characterize chronic heart failure (CHF) and are reflected, in part, as impairment of baroreflex sensitivity (BRS) and sympathetic function. However, the mechanisms that trigger these neurohumoral abnormalities in CHF are not clear. We hypothesized that the BRS is blunted early in CHF and that the humoral effects occur later and contribute to progressive loss of cardiovascular control in CHF. We assessed the BRS (beats/min per mmHg) and recorded renal sympathetic nerve activity (RSNA) in four groups of conscious rabbits at varying time intervals: control, 1-week CHF, 2-week CHF, and 3-week CHF. Chronic heart failure was induced by ventricular pacing at 360 beats/min and was assessed by echocardiography. Arterial blood pressure and heart rate were recorded by an implanted telemetric device and RSNA through an implanted electrode. A significant fall in the ejection fraction, fractional shortening, and an increase in left ventricular end-systolic diameter and left ventricular end-diastolic diameter were observed in all CHF groups. The BRS was significantly reduced in all the CHF groups with no significant change in the basal RSNA (% of maximum) after 1 week of pacing; a small but insignificant rise in RSNA was seen at 2 weeks, and a significant rise in RSNA was observed at 3 weeks. Angiotensin II type 1 (AT-1) receptor protein (Western Blot) and mRNA (reverse transcriptase-polymerase chain reaction) expression in the rostral ventrolateral medulla exhibited a progressive increase with the duration of CHF, reaching significance after 3 weeks, the same time point in which RSNA was significantly elevated. These data are the first to examine early changes in central AT-1 receptors in CHF and suggest that the fall in BRS and hemodynamic changes occur early in the development of CHF followed by sympathoexcitation and overexpression of AT-1 receptors with the progression of CHF, causing further impairment of cardiovascular control.
authors.affiliation: Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska, USA. vpciphysiology@yahoo.com.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Fahim
authors.forename: Lie
authors.initials: L
authors.lastname: Gao
authors.forename: Tarek M
authors.initials: TM
authors.lastname: Mousa
authors.forename: Dongmei
authors.initials: D
authors.lastname: Liu
authors.forename: Kurtis G
authors.initials: KG
authors.lastname: Cornish
authors.forename: Irving H
authors.initials: IH
authors.lastname: Zucker
mesh_terms: D000804:Angiotensin II / Q000097:blood; D000818:Animals; D017704:Baroreflex / Q000502:physiology*; D006333:Heart Failure / Q000209:etiology / Q000503:physiopathology*; D006439:Hemodynamics / Q000502:physiology; D007668:Kidney / Q000294:innervation; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D019255:NADPH Oxidases / Q000096:biosynthesis; D011817:Rabbits; D044140:Receptor, Angiotensin, Type 1 / Q000096:biosynthesis* / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology
chemical_list: D008562:Membrane Glycoproteins; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D019255:NADPH Oxidases