Natriuretic peptide gene expression in DOCA-salt hypertension after blockade of type B endothelin receptor

Abstract

Bianciotti, Liliana G., and Adolfo J. de Bold. Natriuretic peptide gene expression in DOCA-salt hypertension after blockade of type B endothelin receptor. Am J Physiol Heart Circ Physiol 282: H1127-H1134, 2002; 10.1152/ ajpheart.00468.2001.-We investigated the effect of longterm in vivo blockade of the ET-1 receptor subtype B (ET B) with A-192621, a selective ET B antagonist, on atrial and ventricular natriuretic peptide (NP) gene expression in deoxycorticosterone acetate (DOCA)-salt hypertension. In this model, stimulation of the cardiac natriuretic peptide (NP) and the endothelin system and suppression of the reninangiotensin system is observed. DOCA-salt induced significant hypertension, cardiac hypertrophy and increased NP plasma and left atrial and right and left ventricular NP gene expression. ET B blockade per se produced hypertension and left ventricular hypertrophy but induced little change on the levels of ventricular NP and only increased left atrial natriuretic factor (ANF) mRNA levels. Combined ET B blockade/ DOCA-salt treatment worsened hypertension, increased left ventricular hypertrophy and induced right ventricular hypertrophy. All animals so treated had increased ventricular NP gene expression. Collagen III and ␤-myosin heavy chain gene expression were enhanced in both the right and the left ventricle of DOCA-salt hypertensive rats. The results of this study suggest that the ET B receptor does not participate directly in the modulation of atrial or ventricular NP gene expression and that this receptor mediates a protective cardiovascular function. ET B blockade can induce significant ventricular hypertrophy without an increase in ANF or brain NP gene expression. deoxycorticosterone acetate THE LEVEL OF EXPRESSION OF the cardiac natriuretic peptides (NP), atrial natriuretic factor (ANF), and brain natriuretic peptide (BNP), as well as circulating plasma levels, is increased by hemodynamic overload through mechanisms that are believed to involve both mechanical and neuroendocrine stimuli (7). The activation of the cardiac NP system serves to counterbalance the activity of systems that tend to increase extracellular fluid volume and blood pressure such as the renin-angiotensin-aldosterone and sympathetic systems (6). Although much information has been gathered regarding the regulation of NP gene expression and release through in vitro approaches, comparatively little is known regarding the long-term regulation of NP in the heart. Using a model of renovascular hypertension in the rat, we have previously found that there are two components that contribute to chronic increased NP gene expression. One component is independent of load and is concurrent with the hypertrophic process of chronically overloaded hearts whereas the other is dependent on hemodynamic load (26). We also reported that the expression of ANF and BNP in the ventricles and atria is differentially regulated. That is, in the atria, NP expression appears to be governed by mechanical stimuli (atrial muscle stretch) whereas in the ventr...

Concurrent administration of aqueousAzadirachta indica (neem) leaf extract with DOCA-salt prevents the development of hypertension and accompanying electrocardiogram changes in the rat

“…In all ECG parameters (except for the P-wave amplitude) the DOCA-salt-neem group resembled the controls rather than the DOCA-salt group. The high amplitude of QRS complexes is common in DOCA-salt rats and has been attributed to cardiac hypertrophy which is a consequence of the induced hypertension (Matsumara et al, 1995;Bianciotti and De Bold, 2002). In our experiments, DOCA-salt accelerated conduction through the heart and increased the amplitude of the QRS complex and therefore the rate of contraction of the heart.…”

Ventricular hypertrophy and arterial hemodynamics following deprivation of nitric oxide in rats

“…Animal experiments conducted by Arnal et al (1992Arnal et al ( , 1993 revealed in rats that long-term (8 weeks) administration of N N -nitro-arginine methyl ester (l-NAME) significantly reduced the aorta cyclic guanosine monophosphate (cGMP) and elevated the arterial pressure, but did not change the left ventricular weight (LVW) and the LVW to body weight (BW) ratio. The absence of ventricular hypertrophy (VH) contrasted with results obtained in other models of experimental hypertension, in which long-term hypertension was accompanied by overt VH in essential, spontaneous, renovascular and DOCA-salt hypertension or hypertensive disease of primary aldosteronism (Bianciotti and De Bold, 2002;Ehamke et al, 1999;Hu et al, 1994b;Morton et al, 1993;Suzuki et al, 1988;Yokota et al, 1995;Yoshihara et al, 1996).…”

“…This study, in contrast, suggests that the extent of VH induced by chronic l-NAME administration is equally correlated with the steady and pulsatile hemodynamics. The impairment of large vessel properties suggests aortic stiffness and the pulse pressure with stiffness of large vessels was expected to increase (Bianciotti and De Bold, 2002;Hu et al, 1994a;Suzuki et al, 1988;Yoshihara et al, 1996). In these reports, the increase of pulse pressure ranged from 18 B A Fig.…”

Decrease in Hypothalamic Gamma Adducin in Rat Models of Hypertension

“…One DOCA pellet was inserted subcutaneously between the shoulder blades, during which time the left kidney was also removed as described. 17,18 After recovery, rats were maintained on a 1% saline drinking water in place of tap water ad libitum. A control group of SD rats (nϭ6) underwent a sham surgical protocol, and cellulose was implanted instead of a DOCA pellet in parallel with the experimental group.…”