Chronic activation of central alpha2-adrenoceptors prevents hypertension in DOCA-salt rats.

The effects of chronic intracerebroventricular (i.c.v.) injections of the alpha2-adrenoceptor agonist, xylazine, on blood pressure were examined in DOCA-salt rats. Acute studies also examined the renal sympathetic nerve activity (RSNA) and renal excretory responses produced by i.c.v. xylazine in rats with established DOCA-salt hypertension. Rats implanted with a chronic i.c.v. cannula for drug injection were used. In chronic studies, four groups were investigated: control rats treated with s.c. soybean oil and i.c.v. saline; DOCA-salt rats (s.c. deoxycorticosterone acetate) receiving i.c.v. saline, xylazine or the alpha2-adrenoceptor antagonist, yohimbine. During vehicle or DOCA-salt treatment, xylazine (0.2 ng/microg) or yohimbine (10O microg/kg) was injected i.c.v. daily (three times). In DOCA-salt rats receiving i.c.v. saline, resting mean arterial pressure (MAP) was elevated on days 15 and 30 (135 +/- 5 and 160 +/- 6 mmHg, respectively). Chronic i.c.v. xylazine significantly attenuated the rise in MAP produced by DOCA-salt (day 15, 118 +/- 5 mmHg; day 30, 121 +/- 4 mmHg). Alternatively, chronic i.c.v. yohimbine shortened the onset (day 15, 152 +/- 7 mmHg) and augmented the hypertension in DOCA-salt rats (0 survival by day 30). In acute studies, i.c.v. xylazine elicited a profound natriuresis and diuresis as well as a reduction in RSNA without altering MAP. This study demonstrates that the ongoing (tonic) activity of central alpha2-adrenoceptor mechanisms are critically involved in regulating blood pressure in the DOCA-salt treated rat. In this manner, an enhanced activity of central alpha2-adrenoceptor systems acts to protect against a rise in blood pressure. In contrast, the attenuation of central alpha2-adrenoceptor stimulation evokes hypertension. The central action of xylazine to prevent hypertension may be associated with the inhibition of sympathetic outflow to the kidneys and evokes an enhanced natriuresis. By inhibiting the avid sodium retention elicited by DOCA-salt treatment, the central activation of alpha2-adrenoceptors delays the onset and the severity of hypertension in this pathological model.

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

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, s.c.) 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 weighted. 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.

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

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 factores 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 percent NaCl and 0.03 percent 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 percent) 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.