Diverse effects of renal denervation on ventricular hypertrophy and blood pressure in DOCA-salt hypertensive rats

Abstract

Cardiac hypertrophy that accompanies hypertension seems to be a phenomenon of multifactorial origin whose development does not seem to depend on an increased pressure load alone, but also on local growth factors and cardioadrenergic activity. The aim of the present study was to determine if sympathetic renal denervation and its effects on arterial pressure level can prevent cardiac hypertrophy and if it can also delay the onset and attenuate the severity of deoxycorticosterone acetate (DOCA)-salt hypertension. DOCA-salt treatment was initiated in rats seven days after uninephrectomy and contralateral renal denervation or sham renal denervation. DOCA (15 mg/kg, sc) or vehicle (soybean oil, 0.25 ml per animal) was administered twice a week for two weeks. Rats treated with DOCA or vehicle (control) were provided drinking water containing 1% NaCl and 0.03% KCl. At the end of the treatment period, mean arterial pressure (MAP) and heart rate measurements were made in conscious animals. Under ether anesthesia, the heart was removed and the right and left ventricles (including the septum) were separated and weighed. DOCA-salt treatment produced a significant increase in left ventricular weight/body weight (LVW/BW) ratio (2.44 ± 0.09 mg/g) and right ventricular weight/body weight (RVW/BW) ratio (0.53 ± 0.01 mg/g) compared to control (1.92 ± 0.04 and 0.48 ± 0.01 mg/g, respectively) rats. MAP was significantly higher (39%) in DOCA-salt rats. Renal denervation prevented (P>0.05) the development of hypertension in DOCA-salt rats but did not prevent the increase in LVW/BW (2.27 ± 0.03 mg/g) and RVW/BW (0.52 ± 0.01 mg/g). We have shown that the increase in arterial pressure level is not responsible for cardiac hypertrophy, which may be more related to other events associated with DOCA-salt hypertension, such as an increase in cardiac sympathetic activity. Correspondence

Mild DOCA-salt hypertension: sympathetic system and role of renal nerves

“…Osborn and colleagues (25) recently demonstrated that intact renal nerves are crucial for the development of the traditional DOCA-salt model of hypertension, because RDX significantly attenuated hypertension development. Several other investigators have reported similar findings (4,28,49). Therefore, we investigated the effects of RDX in our model of DOCA-salt hypertension.…”

Targeted afferent renal denervation reduces arterial pressure but not renal inflammation in established DOCA-salt hypertension in the rat

“…Role of afferent and efferent renal nerves in mediating the cardiovascular and neural responses to renal denervation in DOCA-salt hypertension. Since the original reports of Katholi and colleagues (24), the sympathetic nervous system, particularly the renal sympathetic nerves, has been known to contribute to DOCA-salt hypertension development and maintenance (3,7,16,19,(22)(23)(24)49). We recently expanded these studies by investigating the individual contributions of efferent and afferent renal nerves during the development of DOCA-salt hypertension (3,16) by comparing the effects of targeted ablation of renal afferent nerves with those observed with total (afferent ϩ efferent) denervation.…”

Renal denervation attenuates cardiac hypertrophy in spontaneously hypertensive rats via regulation of autophagy

“…These observations have been confirmed in subsequent clinical studies ( 18 – 20 ). Interestingly, some animal studies also found similar benefits of RD on cardiac hypertrophy and cardiac remodeling in various animal models ( 21 – 23 ), Mechanisms aside from attenuation of blood pressure and reduction in the activity of sympathetic nerves have been proposed to account for these changes, including a reduction in myocardial inflammation ( 22 ). However, whether RD has the ability to attenuate cardiac hypertrophy, induced by pressure overload of the LV, remains to be confirmed, and the potential mechanisms by which this may occur are not currently known.…”