Selective vasodilation produced by renal denervation in adult spontaneously hypertensive rats.

Abstract

The kidneys of adult male spontaneously hypertensive rats (SHR) were denervated, and systemic and regional blood flows were measured 3 to 5 hours or 5 days after denervation. Arterial pressure was reduced 20 to 27% in denervated SHR during both periods compared with that in sham-operated SHR (iliolumbar blood vessels painted with phenol). This hypotensive response was produced by a 32 to 35% reduction in total peripheral resistance. At 3 to 5 hours and at 5 days, a major decrease in total peripheral resistance was produced by vasodilation in the kidneys and splanchnic organs. Acute urine output, sodium excretion, and plasma renin activity in response to a saline load were not different between sham-operated and denervated SHR. The decreased total peripheral resistance in denervated SHR may have been secondary to a decreased central sympathetic nerve activity revealed by a decreased maximum response to ganglionic blockade. The results suggest that a pathophysiological link may exist between the kidneys and splanchnic organs in genetic hypertension and that specific efferent antiadrenergic or antiafferent nerve therapy, or both, in the kidney may lead to substantial specific decreases not only in renal vascular resistance but also in splanchnic vascular resistance and total peripheral resistance.

Role of afferent renal nerves in spontaneous hypertension in rats.

“…This hypotensive effect of ARN-x is small in comparison with the 20-27% reductions in arterial blood pressure after complete renal denervation in adult SHR. 9 In other reports, however, renal denervation failed to induce a hypotensive effect in SHR when hypertension was established. 8 Nevertheless, our data suggest that the reported hypotensive effects of total renal denervation in young as well as in adult SHR (see 13,14,33) are mainly due to the loss of the ERN.…”

“…To assess the contribution of the sympathetic nervous system tone to the maintenance of blood pressure in these conscious animals, changes in mean arterial pressure and heart rate were recorded (mean of 5-15 minutes) after intravenous injection of 20 mg/kg hexamethonium (Sigma Chemical Co.), which causes total ganglionic blockade in rats. 9 Plasma and tissue norepinephrine determination. Before any drugs were given (day 1) a 0.5 ml arterial blood sample was taken from all rats for determination of plasma norepinephrine levels.…”

“…Krueger et al 9 reported that in adult SHR after complete renal denervation, blood pressure was significantly less dependent on central sympathetic tone. Comparison of our results with these observations suggests that this effect of complete renal denervation is once more mediated through the loss of the ERN.…”

“…Renal denervation may lead to a hypotensive effect through alterations in renal excretory function or renin release. 12 In addition, renal denervation changes hypothalamic norepinephrine content, 13 cardiovascular responses to ganglionic blockade, 9 and electrical hypothalamic stimulation 14 in several experimental hypertensive models. These data suggest that peripheral section of these nerves may alter central sympathetic nervous activity.…”

Renal nerves in blood pressure regulation

“…Indeed, many of the early studies reported that renal denervation slowed or delayed the rise in blood pressure in experimental models of hypertension such as spontaneous hypertension [70][71][72], Dahl hypertension [73 && ], N v -nitro-L-arginine methyl ester (L-NAME) induced hypertension [74], angiotensin II induced hypertension and deoxycorticosterone acetate (DOCA)-salt hypertension [75,76]. This regulatory modulation of blood pressure by the renal sympathetic nerves is further evidenced by the higher sympathetic nerve activity in patients with renal failure conditions [77,78].…”