Atrial natriuretic factor gene expression in rat ventricle during experimental hypertension

Abstract

Activation of atrial natriuretic factor (ANF) gene expression has been reported in the rat ventricle in several models of hemodynamic overload, including hypertension. However, nothing is known about the potential trigger(s) and the time course of this activation during the development of hypertension. We measured aortic blood pressure, left ventricular hypertrophy (LVH), and left ventricular ANF mRNA concentration (LV ANF mRNA) in a first group of rats (study A) killed at 5 and 18 h and 2, 4, 6, 9, 15, and 30 days after suprarenal coarctation of the abdominal aorta. Coarctation induced a progressive rise in aortic blood pressure and left ventricular mass. We observed a biphasic accumulation of ANF mRNA in the left ventricle with a peak at day 4 averaging 20 times the control value long before stable hypertension and hypertrophy were achieved, followed by a decrease until day 9. This decrease was followed by a new rise, which stabilized around 10 times the control value seen during stable hypertension and hypertrophy. In a second group of rats killed at days 4 and 30 (study B), we determined, in addition to the previous parameters, left ventricular end-diastolic pressure (LVEDP), plasma renin (PRC), and plasma ANF concentrations. LVEDP and PRC were markedly increased at day 4, but at day 30, during stable hypertension and hypertrophy, these parameters returned to control values, whereas plasma ANF was increased. Using immunocytochemistry, we looked in a third group of rats (study C) for the presence of the immunoreactive peptide at days 4 and 30.(ABSTRACT TRUNCATED AT 250 WORDS)

Gene expression of atrial natriuretic peptide in rat papillary muscle Rapid induction by mechanical loading

“…In rats ventricular ANP mRNA levels have been shown not to rise before more than 18 h after coarctation of the aorta [4]. A similar time course of expression has been reported for the genes of skeletal ~-actin or fl-isomyosin heavy chain [2,3].…”

“…The gene expression of such fetal proteins in response to hemodynamic stress is relatively slow in onset, taking 1-2 days for contractile proteins such as skeletal ~-actin or flisomyosin heavy chain [2,3]. A similar time course of expression has been reported for the biosynthetic precursor of atrial natriuretic peptide (ANP), another cardiac protein synthesized in response to increased ventricular wall stress [4]. In the adult heart ANP production is confined to the atria and the ventricular impulse conduction system [5].…”

Activation of angiotensinogen and angiotensin-converting enzyme gene expression in the left ventricle of senescent rats.

“…' In the hypertrophied LV, an activation of ANG and ACE gene transcription has been described, suggesting that the expression of these genes could be activated in response to a cardiac overload.15"6 ANF mRNA accumulation is also increased after aortic constriction. 17 Assuming In fact, with aging, a decrease in the coronary blood flow, a loss of myocytes, and hypertrophy of the remaining cells accompanied by an increase in the interstitial collagen content associated with myocardial fibrosis have been reported.1-3'7 Since the collagen concentration is a major determinant for both diastolic compliance and arrhythmias, the increase in collagen concentration observed in the senescent myocardium could explain the elevation in LV stiffness and the high incidence of arrhythmias observed in senescent rats. 5 Indirect evidence for the cardiac and vascular effects of Ang II has been suggested by chronic treatment with ACE inhibitors (ACEI).…”

“…In addition, the hormonal status is also modified and is characterized by a decrease of plasma angiotensin II (Ang II), renin, angiotensinogen (ANG),9 and total triiodothyronine concentrations10 and elevated cortisol and atrial natriuretic factor (ANF) levels, at least in humans. [11][12][13] Recent data demonstrate that, in young adult rats, the myocardium is able to synthesize Ang II from ANG and angiotensin-converting enzyme (ACE).14 Pressure overload results in an increased accumulation of both ANG and ACE mRNAs15, 16 and also in an increased synthesis of ANF, 17,18 suggesting that these gene transcriptions could be activated by mechanical triggers.…”

Left ventricular SERCA2a gene down‐regulation does not parallel ANP gene up‐regulation during post‐MI remodelling in rats

“…In the vast majority of animal models of chronic hemodynamic overload, decreased SERCA2a mRNA levels are paralleled by increased atrial natriuretic peptide (ANP) mRNA levels, a surrogate molecular marker of the degree of myocardial hypertrophy during post-MI LV remodelling [34,35], LV chronic pressure overload [36] and LV volume overload [37]. The concept of an antithetic regulation of the two genes is further supported by the finding by Arai et al of a strong negative linear correlation between SERCA2a and ANP mRNA levels in LV samples obtained from patients with end stage heart failure at the time of transplantation.…”