Diuretic and Natriuretic Responses to Anf in the Presence and Absence of Renal Nerves in Doca-Salt Hypertensive Rats

To determine if renal nerves contributes in the renal response to atrial natriuretic factor (ANF) in DOCA-salt hypertensive rats, diuretic and natriuretic responses to ANF were measured in Inactin (0.1 g/kg, i.p) anesthetized rats with unilateral renal denervation. Rats were assigned to either a control group (108±6 mmHg), or one of two DOCA-salt groups (injected with deoxycorticosterone acetate, DOCA, 25 mg/week, and given 0.9% saline to drink for 4 weeks); a) DOCA-salt group (137±6 mmHg) and b) DOCA-salt-BPC group (with blood pressure controlled at the level of the femoral artery (102±3 mmHg) by an occluder on the abdominal aorta proximal to the right renal artery). Urine flow and sodium excretion in response to ANF infusion (0.3 μg/min/kg) were measured from intact and denervated kidneys of control and DOCA-salt treated rats.

ANF infusion produced a significant increase in diuresis and natriuresis in all three groups of rats. Urine flow and sodium excretion in response to ANF were significantly less in the intact kidney but not the denervated kidneys of the DOCA-salt rats compared to control rats. These results indicate that renal nerves contribute to the blunted renal responses to ANF in DOCA-salt rats. Renal responses also were significantly smaller in both intact and denervated kidneys of DOCA-salt-BPC rats (in which arterial pressure was reduced) compared to DOCA-salt rats. Overall, these results indicate that both renal nerves and arterial pressure determine the natriuretic and diuretic actions of ANF in DOCA-salt hypertensive rats.     

Renal and systemic vascular conductances in renal wrap hypertension in rabbits

The contribution of renal vascular conductance to the fall in total peripheral conductance during the development of renal wrap hypertension was determined in conscious rabbits. Measurements were made 28 days after renal wrap (n = 9) or sham operation (n = 8). Blood pressure was about 50 mmHg higher in the wrapped group as compared to the sham-operated group. This was due to a fall in total peripheral conductance of about 42%. Cardiac output was not significantly different between wrap and sham groups. Renal vascular conductance was 0.42 ml/min per mmHg lower in the wrap compared to the sham-operated group (P less than 0.001). Total peripheral conductance was 3.93 ml/min per mmHg lower in the wrap compared to the sham group (P less than 0.01). The reduction in renal vascular conductance in wrapped rabbits, which is probably due to compression caused by the thickening renal capsule, accounts for about 10% of the fall in total peripheral conductance. We suggest that this mechanically induced reduction in renal conductance is involved in the initiation and maintenance of the hypertension, but is only a minor contributor to the overall change in blood pressure.     

Renal denervation decreases blood pressure and renal tyrosine hydroxylase but does not augment the effect of hypotensive drugs

The effect of renal denervation on the efficacy of antihypertensive drugs has not yet been elucidated. Twenty-week-old spontaneously hypertensive rats were treated with metoprolol, losartan, indapamide, or saline (controls) and assigned to renal denervation or a sham procedure. Acute hemodynamic measurements were performed ten days later. Series showing a significant interaction between renal denervation and the drugs were repeated with chronic telemetry measurements. In the saline series, denervated rats showed a significantly lower mean arterial blood pressure (blood pressure) than the sham-operated rats. In contrast, in the metoprolol series denervated rats showed a significantly higher blood pressure than sham rats. There were no differences in blood pressure between denervated and sham rats in the losartan and indapamide series. In chronic studies, a 4-week treatment with metoprolol caused a decrease in blood pressure. Renal denervation and sham denervation performed 10 days after the onset of metoprolol treatment did not affect blood pressure. Denervated rats showed markedly reduced renal nerve tyrosine hydroxylase levels. In conclusion, renal denervation decreases blood pressure in hypertensive rats. The hypotensive action of metoprolol, indapamide, and losartan is not augmented by renal denervation, suggesting the absence of synergy between renal denervation and the drugs investigated in this study.     

Paradoxical structural effects in the unilaterally denervated spontaneously hypertensive rat kidney

OBJECTIVE: To determine the effects of chronic denervation on renal vascular structure and function in young adult spontaneously hypertensive rats (SHRs). DESIGN: Unilateral renal denervation (SHRUDx) or sham-operation (SHRS) was performed in SHRs at 6 weeks of age. At 10 weeks, rats were allocated to one of three procedures designed to examine renal vascular structure and function. A further group underwent bilateral renal denervation. METHODS: In SHRUDx or SHRS groups, either the kidneys were perfusion-fixed for stereological estimates of artery wall and lumen dimensions or for vascular casting to determine arteriole lumen diameters, or the rats were anaesthetized for estimation of glomerular capillary pressure. RESULTS: Chronic unilateral renal denervation had no significant effect on the development of hypertension between 6 and 10 weeks of age, as previously reported, but resulted in luminal narrowing of the interlobular artery (denervated group 52 +/- 2 mum, sham-operated group 64 +/- 1 mum; P < 0.01 for interaction between strain and treatment), without alterations in interlobular or arcuate artery wall dimensions. There were no significant effects on either afferent or efferent arteriole lumen diameters. Estimated glomerular capillary pressure was significantly lower in the denervated kidneys of SHRUDx (47 +/- 1 mmHg) compared with kidneys of the SHRS (50 +/- 1 mmHg; P < 0.04). Mean arterial pressure was approximately 12 mmHg lower in the bilaterally denervated SHRs than in the sham-operated SHRs. CONCLUSIONS: Although bilateral denervation attenuated the development of hypertension in SHRs, unilateral denervation did not, indicating that one neurally intact kidney was sufficient to drive the normal development of SHR hypertension, but only with apparent prohypertensive compensatory changes in the denervated kidney.     

Effects of nicardipine on the systemic and renal hemodynamics in acutely elevated blood pressure induced by vasoactive agents in conscious rabbits

The effects of the calcium antagonist, nicardipine, on blood pressure and renal hemodynamics were examined in rabbits with norepinephrine- and angiotensin II-induced elevation of blood pressure. With norepinephrine-infusion, the mean arterial pressure increased from 84 +/- 4 to 118 +/- 4 mmHg accompanied by decreases in heart rate (10%) and renal blood flow (45%). In contrast to the changes in renal blood flow with norepinephrine-infusion, renal blood flow following angiotensin II-induced elevation of blood pressure was decreased by more than 60% at the same degree of elevation of mean arterial pressure. Both intravenous and intrarenal administration of nicardipine (1 microgram/kg) reduced the mean arterial pressure and restored the decreased heart rate and renal blood flow in both norepinephrine- and angiotensin II-infused animals. Intrarenal injection of nicardipine decreased the elevated mean arterial pressure of angiotensin II-induced hypertension more than did intravenous injection (16 +/- 2 vs. 11 +/- 3 mmHg, p less than 0.05). Renal nerve denervation did not lead to any significant effects on the mean arterial pressure, heart rate and renal blood flow following intravenous or intrarenal injection of nicardipine in norepinephrine-infused animals. On the other hand, in angiotensin II-induced elevation of blood pressure, the potentiated hypotensive effect of intrarenal injection of nicardipine was lost in renally denervated animals. In conclusion, the calcium antagonist, nicardipine, was shown to reduce the acutely elevated blood pressure caused by norepinephrine or angiotensin II. In angiotensin II-induced elevation of blood pressure, the renal vasculature may play a more important role in both pressor and depressor aspects in the regulation of blood pressure as compared to its role in norepinephrine-induced hypertension.     

Bilateral Renal Denervation Can Prevent the Development of Stress-Induced Hypertension in the Borderline Hypertensive Rat

The borderline hypertensive rat (BHR) shows large blood pressure responses to either stress or a high salt diet. Since the renal nerves have been shown to play a role in several animal models of hypertension, the current study sought to determine the effect of bilateral renal denervation on the development of stress-induced hypertension in the BHR. BHR were deprived of renal nerves under ether anesthesia after either 5 or 11 weeks of daily 2-hour stress sessions. Additional BHR received sham surgery. Unstressed BHR, age-matched to stressed groups, received denervation or sham surgery. Following a 3 week recovery period, the protocol (stress or no stress) was continued for 10 additional weeks. Tail cuff systolic blood pressures were obtained weekly. BHR stressed for 5 weeks prior to denervation failed to develop hypertension in response to continued stress. Although BHR stressed for 11 weeks prior to denervation showed a temporary reduction in pressure following denervation, blood pressure returned to the hypertensive levels of sham-operated controls after several weeks. Thus, there may be a critical period during which the renal nerves are necessary for the expression of stress-induced hypertension in the BHR. These observations are discussed in relation to the effects of renal denervation on hypertension in various animal models.     

Retardation of the development of hypertension in DOCA-salt rats by renal denervation

To determine the importance of the renal nerves in DOCA-salt hypertension, either renal denervation or a sham-operation was carried out on both DOCA-salt-treated and non-DOCA-treated rats. The systolic blood pressure of the non-DOCA rats remained within normotensive levels, in which the difference in blood pressure levels between the renal denervated and the sham-operated groups was not significant. On the other hand, the blood pressure of the rats treated with DOCA, and having intact renal nerves, began to rise by the end of the first week and rose consistently thereafter, whereas, in the renal denervated DOCA-salt rats, the blood pressure started to rise by the second week and then proceeded to increase gradually. The differences between the sham and the denervated rat groups were significant throughout the four weeks. The mean arterial pressure, directly measured from the caudal artery of conscious rats during the fourth week of this study, was 166 +/- 7 mmHg in the sham-operated and 129 +/- 4 mmHg in the renal-denervated rats (the data having an 1% significant difference). To test the effects of renal denervation on the natriuresis, pentobarbital-anesthetized rats were infused intravenously with physiological saline. The renal denervated rats which had received DOCA excreted more sodium than did the sham-operated rats. When the rats were later anesthetized with urethane to allow intracisternal injections of hypertonic saline, the mean blood pressure in renal denervated rat groups was again lower than that of the sham-denervated rat groups. However, subsequent intracisternal injections of 5% saline produced similar pressor responses as well as tachycardia in both DOCA groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Postural hypotension following N-type Ca2+ channel blockade is amplified in experimental hypertension

OBJECTIVE: To determine the relative importance of the cardiac and vascular sympathetic components of the orthostatic response to 90 degrees head-up tilt after N-type calcium-channel blockade in normotensive (sham renal cellophane wrap) and hypertensive (renal wrap) conscious rabbits. METHODS: The effects of N-type calcium-channel blockade with omega-conotoxin GVIA (omega-CTX, 10 microg/kg i.v. bolus) were assessed in the absence or presence of cardiac block by propranolol and methscopolamine. These were contrasted with the effects of alpha1-adrenoceptor antagonism (prazosin 0.5 mg/kg i.v. bolus, in the presence of cardiac block) or ganglion blockade (mecamylamine 4 mg/kg i.v. bolus). RESULTS: In vehicle (0.9% saline) treatment groups, the response to tilt consisted of a small pressor effect (4 +/- 2 and 7 +/- 1 mmHg) and tachycardia (29 +/- 6 and 17 +/- 6 beats/min) in sham (n = 6) and wrap (n = 5) rabbits, respectively. After prazosin administration (with cardiac block), there were significant falls in MAP of 3 +/- 1 and 7 +/- 2 mmHg in sham (n = 7) and wrap (n = 6) rabbits, respectively, in response to tilt omega-CTX caused postural hypotensive responses of 8 +/- 2 and 13 +/- 2 mmHg in sham (n = 6) and wrap (n = 7) rabbits, respectively, and 7 +/- 1 and 14 +/- 2 mmHg in sham (n = 7) and wrap (n = 7) rabbits with prior cardiac block. Similarly, mecamylamine caused falls in MAP of 8 +/- 1 and 10 +/- 2 mmHg in response to tilt in sham (n = 6) and wrap (n = 9) animals, respectively. CONCLUSION:Sympathetic vasoconstrictor effectors are primarily responsible for maintaining blood pressure during tilt in conscious rabbits. The postural hypotension caused by sympatholytic agents is about double in hypertensive rabbits, and N-type calcium-channel blockade is as effective as ganglion blockade at inducing this syndrome.     

Renal Nerve-Mediated Proximal Tubule Solute Reabsorption Contributes to Hypertension in Spontaneously Hypertensive Rats

Renal nerve activity increases (Na⁺, K⁺)-ATPase activity and contributes to the development of hypertension in young SHR. The present study was designed to examine the effect of sodium intake on blood pressure and proximal tubule solute reabsorption in sham-operated or renal denervated, 5-week old SHR and WKY. Three-week old SHR and WKY rats underwent sham surgery or renal denervation with 10% phenol and were maintained for 10 days on either a 0.6% or 2.2% NaCl diet. Blood pressure was obtained by indirect tail cuff measurements during this interval. Of the eight groups, only sham-operated SHR on a high sodium diet had hypertension, 122.0 × 4.2 mm Hg vs. 98.7 × 3.3 mm Hg (mean for remaining groups). Renal plasma flow (RPF), glomerular filtration rate (GFR), and the fractional excretion of lithium (FE_Lj) were determined in rats maintained on a 2.2% sodium diet at 5 weeks of age. FE_li was less in sham-operated SHR, 5.3 × 0.7%, compared to WKY, 9.4 × 2.8% (P>0.02). Furthermore, denervation ameliorated the reduced FE_Li in SHR, 10.2 × 1.2%, without affecting FE_Li in WKY. RPF and GFR were similar between sham-operated and renal denervated SHR and WKY. No significant difference could be detected in net sodium balance between WKY and SHR during this period. These findings demonstrate 1) from the basis of FE_Li, young SHR, of this strain, exhibit enhanced proximal tubule solute reabsorption and hypertension while on a high sodium diet and, 2) renal denervation ameliorates both the enhanced proximal tubule solute reabsorption and the early development of hypertension. These data support the concept that renal nerve activity of young SHR is augmented and contributes to the development of hypertension by enhancing salt retention.     

Functional Evidence of Inhibitory Reno-renal Reflexes in Spontaneously Hypertensive Rats

The experiments were performed to study the role of the renal nerves and the reno-renal reflexes in the control of water and sodium excretion in spontaneously hypertensive rats (SHR) compared to their normotensive controls, Wistar Kyoto (WKY) rats. Unilateral renal denervation in anaesthetized animals produced a slight, progressive decrease in arterial pressure in both WKY and SHR rats. The glomerular filtration rate temporarily increased in the kidney that underwent the denervation in the SHR group only. After unilateral renal denervation a sharp increase in water and sodium excretion from the ipsilateral kidney was observed in both WKY and SHR. One hour after the denervation, the percent changes in water and sodium excretion were smaller in WKY (+32 ± 19% and +24 ± 17%) than in SHR rats (+84 ± 15% and +93 ± 20%). In the kidney contralateral to the denervation a reduction in water and sodium excretion was observed and this reduction was prompter in SHR than in WKY rats. One hour after the denervation, the percent changes in water and sodium excretion were similar in WKY (-21 ± 8% and -18 ± 7%) and SHR (-19 ± 6% and -19 ± 7%). In control groups, sham denervation did not cause significant changes in glomerular filtration rate, and urinary water and sodium excretion. Arterial pressure slightly and progressively decreased in both control groups. Electrical stimulation of the efferent renal nerves performed in WKY and SHR produced similar decreases in renal blood flow, glomerular filtration rate, and water and sodium excretion in the two groups for the same frequencies of stimulation. As this finding indicates that renal targets in hypertensive rats are normally responsive to the neural drive, our data demonstrate that renal responses to unilateral renal denervation in hypertensive rats are equal to the responses observed in normotensive rats. Our results indicate that tonically active inhibitory reno-renal reflexes normally operate in spontaneously hypertensive rats.     

Renin activity and blood pressure in response to chronic episodic hypoxia.

Previous studies in several strains of rats have demonstrated that 35 days of recurrent episodic hypoxia (EH) (7 hours per day), with a fractional concentration of inspired oxygen that produces desaturation equivalent to the recurrent hypoxemia of sleep apnea, results in an 8 to 13 mm Hg persistent increase in diurnal systemic blood pressure (BP). Carotid chemoreceptors and the sympathetic nervous system have been shown to be necessary for development of this BP increase. Both renal artery denervation and adrenal demedullation block the BP response to chronic EH. The present study was undertaken to define further the role of the kidneys and the renin-angiotensin system in this BP increase. Separate groups of male Sprague-Dawley rats had either (1) bilateral renal artery denervation with EH, (2) sham surgery with EH, (3) sham surgery with sham EH (compressed air), (4) EH with losartan, (5) unhandled with losartan, or (6) unhandled. The experimental period lasted 35 days. Both renal-artery denervated and losartan-treated animals showed no BP change or a lowering of BP in response to EH, whereas the sham-operated EH animals showed a progressive, sustained increase in resting room air BP. BP remained at basal levels or fell in unhandled and unhandled losartan-treated animals. Plasma renin activity was elevated 4-fold versus basal levels in EH animals with renal nerves intact but remained at baseline levels in denervated animals. At the end of the experiment, renal tissue catecholamines confirmed renal denervation in those animals. In conclusion, EH causes a progressive increase in BP, mediated in part through renal sympathetic nerve activity that acts to increase renin-angiotensin system activity through angiotensin II type 1 receptors.     

Inositol phosphate formation in arterial smooth muscle from rabbits with perinephritis hypertension

Total inositol phosphate formation was measured in the aorta and femoral artery from rabbits at 1, 2 and 6 weeks after kidney wrapping, at which times the mean arterial pressures were 88 +/- 4, 96 +/- 3 and 126 +/- 7 mmHg against a control pressure of 74 +/- 3 mmHg. Noradrenaline-stimulated (10(-7) to 10(-4) mol/l) inositol phosphate formation was increased in the aorta and femoral artery from hypertensive rabbits at 2 weeks (aorta noradrenaline 10(-6) mol/l sham, 105 +/- 14%; hypertensive, 164 +/- 20% of control). Noradrenaline-stimulated inositol phosphate formation was unchanged at 1 and 6 weeks in the aorta. Endothelin-stimulated inositol phosphate formation was unchanged at 2 weeks. Basal inositol phosphate formation was not significantly different in normotensive and hypertensive animals. In perinephritis hypertension there is an alteration in phosphatidylinositol metabolism in arterial smooth muscle. This occurs at the time when the blood pressure is rising rapidly. This alteration may affect a specific phosphatidylinositol pool that is linked to the alpha-adrenoceptor but not to the endothelin receptor.     

Circulating digoxin-like immunoreactivity in renal hypertensive rabbits: lack of modulation by alterations in dietary sodium intake

We have re-examined digoxin-like immunoreactivity, commonly detected in plasma with antibodies, in order to determine whether it could represent the putative natriuretic factor originally proposed by de Wardener and Clarkson. Experiments were conducted in adult rabbits with two-kidney, two wrapped hypertension and in sham-operated controls. Six weeks after the bilateral renal cellophane wrapping or sham operation, the mean arterial pressure (MAP) was approximately 40 mmHg higher in the wrapped group. At this time the rabbits started a low-, normal- or high-salt diet (1.6, 25.6 and 40.8 mmol Na+/100 g) which continued for 2 weeks. During the final 3 days urinary volume and total sodium content measured in 24-h collections was significantly lowered in the rabbits on the low-salt diet and increased by the high-salt diet (P less than 0.01 for both). This pattern was identical for the normotensive and renal hypertensive rabbits. Digoxin-like immunoreactivity was measured at the beginning and at the end of the 2-week period of the salt study. Immediately before commencing the various salt diets the digoxin-like immunoreactivity, measured as ng digoxin equivalents/ml, was only marginally elevated in the renal hypertensive compared to the normotensive animals (it averaged 94.7 +/- 7.7 and 80.9 +/- 5.9 ng digoxin equivalents/ml, respectively). Neither the low- nor the high-sodium diet affected plasma digoxin-like immunoreactivity in either the normotensive or the renal hypertensive animals (P greater than 0.10). These results indicate that digoxin-like immunoreactivity is present in the plasma of normotensive and renal hypertensive rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)     

EFFECT OF NITRIC OXIDE INHIBITION ON KIDNEY FUNCTION IN EXPERIMENTAL RENOVASCULAR HYPERTENSION

We examined the effect of acute systemic blockade of nitric oxide (N0) synthesis on blood pressure and renal function in rats with angiotensin II dependent two-kidney, one-clip Goldblatt hypertension. Hypertensive animals had significantly higher blood pressures, plasma NO metabolite concentrations and urinary NO metabolite excretion rates than control rats. Intravenous administration of N^G-nitro-L-arginine methylester (L-NAME) (10 mg/kg) increased mean arterial pressure in both hypertensive and control animals with the magnitude of increase being greater in hypertensive than control rats (32±3 vs. 20±2 mmHg,p< 0.05). L-NAME did not affect glomerular filtration rates of normal and clipped kidneys but significantly decreased non-clipped kidney glomerular filtration rate (1.1±0.1 vs. 0.7±0.1 ml/min per g kidney wt, p< 0.05). Blood flow to normal and non-clipped kidneys fell in response to L-NAME. Percent reduction in renal blood flow produced by L-NAME was significantly greater in non-clipped than normal kidneys (38±3 vs. 24±2%,p< 0.05). In contrast, clipped kidney blood flow increased after L-NAME (3.3±0.2 vs. 4.0±0.2 ml/min per g kidney wt,p< 0.05). An identical improvement in clipped kidney blood flow occurred when arterial pressure was raised with aortic constriction indicating that the systemic pressor effect of L-NAME was responsible for this finding. These results indicate that NO plays an important role in systemic and non-clipped kidney hemodynamics in renovascular hypertension. Because NO has little influence on stenotic kidney function, the stimulus for increased NO system activity in this disease appears to be vascular shear stress rather than elevated circulating or intrarenal angiotensin II concentrations.     

Renal nerves and the pathogenesis of angiotensin-induced hypertension

The present study examined the role of the renal nerves in the development of hypertension produced by chronic infusion of angiotensin II in the conscious rat. The animals were divided into four groups, and a unilateral nephrectomy was performed. The remaining kidney was denervated in two groups, whereas in the other two groups of animals the nerves were left intact. Four days later either angiotensin II (83 ng/min) or saline infusions were begun through subcutaneously implanted osmotic minipumps. The rats were subsequently studied for 14 days. The results indicate that renal denervation significantly attenuated the pressor response to angiotensin II for approximately 6 days. Following this period, there was no difference in blood pressure between the innervated and denervated rats infused with angiotensin II, as both groups attained a hypertensive level of 170 to 180 mm Hg, which was 60 to 70 mm Hg above the blood pressure of the control rats infused with saline. Kidney norepinephrine content was reduced 95% by the denervation procedure and by 40% following infusion of angiotensin II into rats with intact renal nerves. These data demonstrate that, while the renal nerves appear to play a modulatory role in the development of the hypertension, they are not essential for the pathogenesis to occur nor do they determine the final level of hypertension achieved following chronic infusion of angiotensin II in the rat.     

Plasma vasopressin concentration in high sodium renal hypertension

One-kidney, figure-8 renal wrapped and sham-operated rats maintained on high sodium intake were studied to determine plasma concentrations of vasopressin during the onset of hypertension. Animals were chronically prepared with femoral artery and vein catheters. Arterial blood samples were taken from conscious rats before and 3 days after renal wrap or sham operation while donor blood was simultaneously infused intravenously. Three days after surgery, arterial pressure, plasma osmolality and plasma vasopressin concentration increased significantly in the renal wrapped animals and remained unchanged in the sham-operated rats. Ganglionic blockade with hexamethonium and atropine produced equivalent decreases in arterial pressure and increases in plasma vasopressin concentration in the two groups of rats. Subsequent administration of the V1 vasopressin antagonist, d(CH2)5Tyr(Me)AVP, caused a significantly greater fall in arterial pressure in the hypertensive rats. These results provide further evidence for a contribution of vasopressin to sodium-dependent hypertension.     

Role of pressure in angiotensin II-induced renal injury: chronic servo-control of renal perfusion pressure in rats

Renal perfusion pressure was servo-controlled chronically in rats to quantify the relative contribution of elevated arterial pressure versus angiotensin II (Ang II) on the induction of renal injury in Ang II-induced hypertension. Sprague-Dawley rats fed a 4% salt diet were administered Ang II for 14 days (25 ng/kg per minute IV; saline only for sham rats), and the renal perfusion pressure to the left kidney was continuously servo-controlled to maintain a normal pressure in that kidney throughout the period of hypertension. An aortic occluder was implanted around the aorta between the two renal arteries and carotid and femoral arterial pressure were measured continuously throughout the experiment to determine uncontrolled and controlled renal perfusion pressure, respectively. Renal perfusion pressure of uncontrolled, controlled, and sham kidneys over the period of Ang II or saline infusion averaged 152.6+/-7.0, 117.4+/-3.5, and 110.7+/-2.2 mm Hg, respectively. The high-pressure uncontrolled kidneys exhibited tubular necrosis and interstitial fibrosis, especially prominent in the outer medullary region. Regional glomerular sclerosis and interlobular artery injury were also pronounced. Controlled kidneys were significantly protected from interlobular artery injury, juxtamedullary glomeruli injury, tubular necrosis, and interstitial fibrosis as determined by comparing the level of injury. Glomerular injury was not prevented in the outer cortex. Transforming growth factor (TGF)-beta and active NF-kappaB proteins determined by immunohistochemistry were colocalized in the uncontrolled kidney in regions of interstitial fibrosis. We conclude that the preferential juxtamedullary injury found in Ang II hypertension is largely induced by pressure and is probably mediated through the TGF-beta and NF-kappaB pathway.     

Catheter-based renal denervation in Chinese patients with chronic kidney disease and uncontrolled hypertension

Sympathetic activation contributes to the progression of hypertension and chronic kidney disease (CKD). Ablation of renal sympathetic nerves lowers blood pressure (BP) and preserves renal function in patients with CKD and uncontrolled hypertension by reducing sympathetic nerve activity. But whether this approach is safe and effective in Chinese patients with CKD is unknown. We performed an observational study of eight patients with CKD stages from 1 to 5, office BP ≥150/90 mmHg, while on at least three antihypertensive drug classes including a diuretic, and diagnosis confirmed by 24 h ambulatory systolic BP measurement ≥135 mmHg. All patients underwent catheter-based renal denervation (RDN) using a newly designed RDN System (Golden Leaf Medtech, Shanghai, China). For up to 6 months after RDN, BP was monitored and renal function was assessed. Mean baseline office BP was 165.0 ± 13.9/97.8 ± 5.5 mmHg, despite treatment with three antihypertensive drugs. Six months after RDN, office BP was reduced by 22.1 ± 12.0 (P = .002)/11.0 ± 8.8 mmHg (P = .012) and average 24 h ambulatory BP by 18 ± 13.7 (P = .01)/9.3 ± 7.7 mmHg (P = .016). After RDN, heart rate and estimated glomerular filtration rate (GFR) had no significant change compared with before RDN. In Chinese patients with CKD, our observational pilot study found that treating hypertension with RDN lowers BP while not affecting renal function. Brief Abstract: We performed RDN in eight Chinese patients with hypertension and CKD. The results showed that RDN lowered blood pressure of these patients significantly and eGFR was stable. No obvious adverse event was observed.     

Renal denervation in a patient with prior renal artery stenting

This is a case report of a 69‐year‐old female with treatment‐resistant severe arterial hypertension despite prior successful percutaneous intervention to both renal arteries for significant renal artery stenoses (stenting of the right and balloon angioplasty of the left renal artery). The office blood pressure was 221/108 mm Hg at baseline. Secondary hypertension was ruled out and catheter‐based renal denervation performed (distal to the stent in the right renal artery and in the usual fashion in the left renal artery) without complications. The office blood pressure decreased at 1‐ and 3‐month follow‐up to 185/93 mm Hg and 182/95 mm Hg, respectively. This case illustrates the feasibility and potential efficacy of catheter‐based renal denervation in patients with a renal artery stent, an important finding as persistent hypertension is common in patients despite successful renal artery stenting and currently available trials examining renal denervation have excluded patients with prior renal artery stents. © 2012 Wiley Periodicals, Inc.     

Resistant hypertension: is renal denervation the current treatment of choice?

Background: Resistant hypertension is simply defined as failure to control blood pressure <140/90?mmHg in an adherent non-diabetic patient with normal kidney function despite the use of optimal doses of three antihypertensive agents, including a diuretic. Also, control of blood pressure in any adherent patient with more than four antihypertensive agents defines resistant hypertension. In a patient with diabetes or chronic kidney disease, the goal blood pressure is <130/80?mmHg. One of the most important pathophysiological mechanisms of resistant hypertension is overactivity of the sympathetic nervous system (SNS). In selected patients with resistant hypertension, renal denervation has been shown to control blood pressure by suppressing SNS overactivity. Summary: This review summarizes the results of the studies of renal denervation for resistant hypertension and suggests the use of this procedure in several other conditions that are associated with SNS overactivity. Key message: Renal denervation seems to control blood pressure in patients with resistant hypertension.