Bilateral renal denervation prevents the development of hypertension during diet‐induced obesity in male rats

Abstract

Feeding a moderately high-fat (MHF) diet in male Sprague-Dawley rats induces obesity, pressure natriuresis impairment and hypertension. This study investigated the role of the renal nerves in the impaired pressure natriuresis and hypertension caused by feeding a MHF diet. After collecting baseline data on day 0, 12 rats remained on a low-fat diet (LF group) while the others were switched onto a MHF diet and diverged into obesity-resistant (OR) or obesity-prone (OP). After 4 weeks, half of the OR and OP rats underwent bilateral renal denervation (BRD) to generate four groups: OR, OR/BRD, OP and OP/BRD (n = 12). During 10 weeks, body weight, obesity index, systolic pressure and renal excretory function were measured regularly. After 10 weeks, renal excretory responses to acute salt loading and renal autoregulation were evaluated. The OP and OP/BRD groups had greater increases of body weight and obesity index during the dietary period compared to the other groups, and by week 10 their body weight (425.1 ± 7.2 and 411.9 ± 5.1 g) became considerably larger than that of the LF group (358.5 ± 6.2 g). Renal sodium excretion was reduced by ∼20% at week 4 in the OP and OP/BRD groups, while only the OP group had lower sodium excretion at weeks 6-8 and higher systolic pressure over weeks 5-10 than the other groups and its week 10 systolic pressure reached 138.1 ± 6.7 versus 123.6 ± 2.7 mmHg of the LF group. The OP group showed delayed renal excretory responses to salt loading with rightward and downward shifts in renal autoregulatory curves. Therefore, the renal nerves exert a main mediatory role in the development of pressure natriuresis impairment and hypertension as obesity is established due to the long-term consumption of the MHF diet in male OP rats.

Transmission of high arterial pressure into renal microvessels during venous‐clamping augments ischaemia/reperfusion‐induced acute kidney injury in anaesthetized rats

“…Then, around the aorta rostral to the level of the renal arteries was gently cleared to pass a thread. In the VIR‐rRPP group, this thread was connected to an adjustable screw device that was used for constricting the aorta and reducing RPP to the desired value 10,11 …”

“…In the Sham group, all surgical procedures including cannulations, separating renal artery and vein in both kidneys, and clearing around the aorta were performed, but bilateral renal ischaemia was not induced. Following ischaemic period or equivalent period in the Sham group, the probe (MA1PRB) of a transonic perivascular flowmeter (T402‐PB; Transonic System Inc., Ithaca, NY, USA) was put around the left renal artery to measure renal blood flow (RBF) by the PowerLab 11,12 . The animal was allowed to have more than 1‐h rest, and then there was a 30‐min clearance period over the 1.5–2 h of the reperfusion period.…”

“…In the VIR-rRPP group, this thread was connected to an adjustable screw device that was used for constricting the aorta and reducing RPP to the desired value. 10,11 Following a 15 min of equilibration, both renal veins in the VIR and VIR-rRPP groups were occluded using non-traumatic clamps for 30 min, during which RPP in the VIR-rRPP group was reduced to 50 ± 3 mmHg and recorded by the PowerLab. After the release of clamps in both ischaemic groups and aortic constriction in the VIR-rRPP group, the blood reflow was confirmed by the return of kidney colour to normal.…”

“…Following ischaemic period or equivalent period in the Sham group, the probe (MA1PRB) of a transonic perivascular flowmeter (T402-PB; Transonic System Inc., Ithaca, NY, USA) was put around the left renal artery to measure renal blood flow (RBF) by the PowerLab. 11,12 The animal was allowed to have more than 1-h rest, and then there was a 30-min clearance period over the 1.5-2 h of the reperfusion period. During the clearance period, urine was collected in a pre-weighed Eppendorf tube, and RBF, arterial pressure and heart rate were recorded by the PowerLab.…”