Effect of episodic hypoxia on sympathetic activity and blood pressure

One of the major manifestations of obstructive sleep apnea (OSA) is profound and repeated (episodic) hypoxia during sleep. Acute hypoxia leads to stimulation of the peripheral chemoreceptors, which in turn directly increase sympathetic outflow. It is believed that this increase in sympathetic outflow is directly responsible, at least in part, for the acute blood pressure (BP) changes seen in OSA. It is difficult however, to study the chronic effects of repeated episodic hypoxia (EH) in humans since the chronic cardiovascular changes may take many years to manifest. For this reason, we developed a method of providing recurrent short periods of hypoxia (resembling the episodic desaturation in humans with OSA) to rats for 35 days, stimulating the chemoreceptors and the sympathetic nervous system, allowing examination of the chronic cardiovascular response to EH. The result of EH in rats is a 10-14 mmHg increase in resting (unstimulated) mean BP that lasts for several weeks after cessation of the daily EH. This BP increase is blocked by carotid body denervation, sympathetic nerve ablation, renal sympathectomy, adrenal medullectomy, and the angiotensin-1 receptor blocker losartan. Thus, it appears that adrenergic and renin-angiotensin system over-activity contribute to the early chronic elevated BP in EH and perhaps in human hypertension associated with OSA.     

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.     

Effect of Renal Denervation on the Development of Cellophane-Wrap Hypertension in Rabbits

The development of hypertension in rabbits with bilateral cellophane wrapping of the kidneys was studied in animals with and without surgical denervatton of the kidneys. Mean arterial pressure was measured before and 14 and 28 days after surgery. After 14 and 28 days of wrapping, mean arterial pressure had increased 12 ± 3 mmHg and 31 ± 3 mmHg in rabbits with innervated kidneys and 7 ± 2 mmHg and 26 ± 2 mmHg in rabbits with denervated kidneys, respectively. The increases in arterial pressure were significantly less in the denervated animals. In sham wrap animals, renal denervation also resulted in significantly lower arterial pressure than in sham wrap+sham denervated rabbits. Noradrenaline concentration of denervated kidneys averaged only 4% of that measured in kidneys subjected to sham denervation. The results show that renal denervation slightly attenuated the degree of hypertension developed following renal wrapping. Since renal denervation produced a similar small decrease in arterial pressure in normotensive rabbits it is suggested that the effect is non-specific and probably due to loss of efferent renal sympathetic nerves.     

Sympathetic denervation blocks blood pressure elevation in episodic hypoxia.

We have previously described a rat model that responds to repetitive episodic hypoxia (FiO2 nadir 3-5% for 12 seconds every 30 seconds for 7 hr/day for 35 days) with chronic increase in arterial blood pressure. The purpose of the current study was to determine if peripheral sympathetic nervous system denervation blocks this persistent blood pressure elevation. Chemical sympathetic denervation was achieved and maintained by three intraperitoneal injections (100 mg/kg 6-hydroxydopamine) on days 1, 3, and 27 of a 47-day experiment in two groups of rats. One denervated group was subjected to episodic hypoxia for 40 consecutive days beginning on day 7 and the other remained unhandled in their usual cages. A third group was injected with vehicle only and subjected to the same episodic hypoxia while a fourth group remained unhandled for 40 days. The vehicle-treated, episodic hypoxia-exposed group showed a 7.7 mm Hg increase in mean arterial blood pressure (conscious, unrestrained) over the 40-day period, whereas all other groups showed a decrease in mean arterial pressure. The left ventricle and septum/whole body weight ratio was higher in both episodic hypoxia-exposed groups at the end of the study. Plasma epinephrine in both groups administered 6-hydroxydopamine was higher on day 6 than in the vehicle-injected rats. Measurement of catecholamines in cardiac muscle homogenate confirmed denervation in 6-hydroxydopamine animals. These results indicate that the peripheral sympathetic nervous system is necessary for the persistent increase in blood pressure in response to repetitive episodic hypoxia.     

Intravenous cyclosporine activates afferent and efferent renal nerves and causes sodium retention in innervated kidneys in rats.

The effect of acute intravenous infusion of cyclosporine (10 mg/kg) on efferent renal and genitofemoral nerve activity and afferent renal nerve activity was studied in anesthetized rats. All animals were studied after unilateral renal denervation and extracellular fluid volume expansion. Activity of both efferent sympathetic nerves was increased significantly by cyclosporine infusion (renal, 69%; genitofemoral, 60%). Afferent renal nerve activity was increased 82% after cyclosporine (P less than 0.05). Urine flow rate and both absolute and fractional sodium excretion from the innervated kidney were reduced 50% after cyclosporine infusion (P less than 0.01). Absolute and fractional sodium excretion from the denervated kidney were significantly increased after cyclosporine. Infusion of vehicle had no significant effect on any measured variable in innervated or denervated kidneys. These studies demonstrate the capacity of cyclosporine to increase efferent sympathetic nerve activity and afferent nerve activity. It is also shown that sodium retention resulting from acute infusion of cyclosporine can be attributed to the increase in efferent renal nerve activity.     

Decrease in Sympathetic Nervous System Activity and Attenuation in Response to Stress Following Renal Denervation in the One-kidney One-clip Goldblatt Hypertensive Rat

We have found that renal denervation in the one-kidney one-clip Goldblatt hypertensive rat results in an attenuation of the hypertension associated with a decrease in sympathetic nervous system activity. To test further the hypothesis that the renal nerves (afferents) contribute to the maintenance of hypertension in this model by modulating sympathetic nervous system activity, plasma norepinephrine and epinephrine changes in response to stress were compared in hypertensive sham-operated (n=6), renal denervated (n=6) and control (n=7) animals. Stress was produced in conscious resting unrestrained animals by administering two brief electrical stimulations to the hindlimb. Resting plasma norepinephrine was significantly higher (P < 0.01) in hypertensive sham-operated (420 + 41 pg/ml) compared to renal denervated (289 ± 23 pg/ml) or control (296 ± 25 pg/ml) animals. There was no difference in resting plasma epinephrine among the groups. In response to stress there were significantly greater absolute increases in plasma norepinephrine and epinephrine in hypertensive sham-operated animals compared to renal denervated and control groups, suggesting that the one-kidney one-clip rat exhibits an enhanced sympathoadrenal response to stress. The response to stress in renal denervated rats was the same as that in the control group. Taken together, these data support the concept that the renal afferent nerves modulate sympathetic nervous system activity in the one-kidney one-clip hypertensive rat.     

Central angiotensin type 1 receptor blockade decreases cardiac but not renal sympathetic nerve activity in heart failure

In heart failure (HF), cardiac sympathetic nerve activity (SNA; CSNA) is increased, which has detrimental effects on the heart and promotes arrhythmias and sudden death. There is evidence that the central renin-angiotensin system plays an important role in stimulating renal SNA in HF. Because SNA to individual organs is differentially controlled, we have investigated whether central angiotensin receptor blockade decreases CSNA in HF. We simultaneously recorded CSNA and renal SNA in conscious normal sheep and in sheep with HF induced by rapid ventricular pacing (ejection fraction: <40%). The effect of blockade of central angiotensin type 1 receptors by intracerebroventricular infusion of losartan (1 mg/h for 5 hours) on resting levels and baroreflex control of CSNA and renal SNA were determined. In addition, the levels of angiotensin receptors in central autonomic nuclei were determined using autoradiography. Sheep in HF had a large increase in CSNA (43±2 to 88±3 bursts per 100 heart beats; P<0.05) and heart rate, with no effect on renal SNA. In HF, central infusion of losartan for 5 hours significantly reduced the baseline levels of CSNA (to 69±5 bursts per 100 heart beats) and heart rate. Losartan had no effect in normal animals. In HF, angiotensin receptor levels were increased in the paraventricular nucleus and supraoptic nucleus but reduced in the area postrema and nucleus tractus solitarius. In summary, infusion of losartan reduced the elevated levels of CNSA in an ovine model of HF, indicating that central angiotensin receptors play a critical role in stimulating the increased sympathetic activity to the heart.     

Central baroreflex regulation by the renal nerves in anesthetized rats

To determine whether the renal nerves affect central baroreflex regulation, the aortic depressor nerve (ADN) was stimulated electrically, while blood pressure, heart rate, and splanchnic nerve activity were recorded in renal denervated and sham-operated rats anesthetized with urethane. Tail cuff systolic pressure fell 6 days after renal denervation, but mean blood pressure recorded after anesthetizing with urethane did not differ between renal denervated and sham-operated rats. Urinary sodium excretion was greater in renal denervated than in sham-operated rats. ADN stimulation produced frequency-dependent falls in blood pressure accompanied by inhibitions of sympathetic nerve activity and heart rate. Depressor and sympathetic inhibitory responses to ADN stimulation were significantly smaller in renal denervated than in sham-operated rats. These findings suggest that the renal nerves can regulate baroreflexes centrally.     

Cardiopulmonary and sinoaortic baroreceptors and volume expansion in the monkey

Summary Experiments were performed to determine the effect of combined cardiopulmonary and sinoaortic baroreceptor denervation on the renal responses of the anesthetized nonhuman primate to acute intravascular volume expansion. Adult maleMacaca fascicularis monkeys underwent chronic bilateral thoracic sympathectomy (middle cervical ganglion-T₆) or sham surgery performed in two stages. After a 1–3 week recovery period, each animal was anesthetized with sodium pentobarbital and subjected to cervical vagotomy-sinoaortic denervation or further sham denervation. Estimated blood volume was then acutely expanded 20% with 6% dextran in isotonic saline. Control renal excretory function did not differ between the two groups, and both groups had similar increases in urine flow, sodium excretion, osmolar clearance, free water clearance and renal plasma flow after volume expansion. The patterns of the responses showed some group differences in that the increases in renal excretion after volume-loading had an earlier onset in the denervated animals. These results demonstrate that combined ablation of thoracic sympathetic, vagal and sinoaortic neural pathways does not compromise the ability of the nonhuman primate to increase salt and water excretion when blood volume is acutely expanded. Therefore, these neural mechanisms are not necessary for eliciting the renal responses to this hypervolemic stimulus in this species during the anesthetized state.Supported by NIH Grant No. HL31987Recipient of a Research Career Development Award (HL01383) from the National Heart, Lung and Blood Institute     

Nervous kidney. Interaction between renal sympathetic nerves and the renin-angiotensin system in the control of renal function

Increases in renal sympathetic nerve activity regulate the functions of the nephron, the vasculature, and the renin-containing juxtaglomerular granular cells. Because increased activity of the renin-angiotensin system can also influence nephron and vascular function, it is important to understand the interactions between the renal sympathetic nerves and the renin-angiotensin system in the control of renal function. These interactions can be intrarenal, for example, the direct (by specific innervation) and indirect (by angiotensin II) contributions of increased renal sympathetic nerve activity to the regulation of renal function. The effects of increased renal sympathetic nerve activity on renal function are attenuated when the activity of the renin-angiotensin system is suppressed or antagonized with ACE inhibitors or angiotensin II-type AT(1)-receptor antagonists. The effects of intrarenal administration of angiotensin II are attenuated after renal denervation. These interactions can also be extrarenal, for example, in the central nervous system, wherein renal sympathetic nerve activity and its arterial baroreflex control are modulated by changes in activity of the renin-angiotensin system. In addition to the circumventricular organs, whose permeable blood-brain barrier permits interactions with circulating angiotensin II, there are interactions at sites behind the blood-brain barrier that depend on the influence of local angiotensin II. The responses to central administration of angiotensin II-type AT(1)-receptor antagonists into the ventricular system or microinjected into the rostral ventrolateral medulla are modulated by changes in activity of the renin-angiotensin system produced by physiological changes in dietary sodium intake. Similar modulation is observed in pathophysiological models wherein activity of both the renin-angiotensin and sympathetic nervous systems is increased (eg, congestive heart failure). Thus, both renal and extrarenal sites of interaction between the renin-angiotensin system and renal sympathetic nerve activity are involved in influencing the neural control of renal function.     

Angiotensin-II acts centrally to alter renal sympathetic nerve activity and the intrarenal renin-angiotensin system.

STUDY OBJECTIVE--The aim was to evaluate the influence that centrally administered angiotensin-II has on the intrarenal renin-angiotensin system and renal sympathetic nerve activity. DESIGN--Renal responses to centrally administered angiotensin-II (10 micrograms) or saralasin (50 micrograms) were measured in anaesthetised rats. The right kidney was vascularly isolated (but neurally intact) and perfused with artificial plasma at either a constant pressure (13.3 kPa) or constant flow (600 microliters.min-1) and renal vascular resistance was measured. Renal perfusate was collected at 10 min intervals after central administration of peptides and intrarenal concentrations of noradrenaline and renin were determined. SUBJECTS--Adult female Sprague-Dawley rats (200-225 g) were used. Rats were given thermal (or sham) lesions of the medial basal forebrain (MBF) 24 h prior to renal perfusion studies. RESULTS--Sham lesioned animals: central administration of angiotensin-II caused an increase in renal vascular resistance and intrarenal noradrenaline concentration in both the constant pressure and constant flow renal perfusion models. Central administration of angiotensin-II increased intrarenal renin concentration in the constant pressure model, while it decreased intrarenal renin concentration in the constant flow model. These effects of intracerebroventricular angiotensin-II were blocked by the concomitant administration of saralasin. Saralasin had no agonist actions on the responses measured. Medial basal forebrain lesioned animals: baseline levels of intrarenal noradrenaline concentration in both the constant flow and constant pressure perfusion models were significantly reduced compared to sham lesioned rats. Baseline intrarenal renin concentration was increased relative to sham lesioned rats in the constant flow perfusion model, but decreased relative to sham lesioned rats in the constant pressure perfusion model. Lesions of the medial basal forebrain block responses to intracerebroventricular angiotensin-II in both models. CONCLUSIONS--Angiotensin-II appears to act on neurones within the medial basal forebrain to increase renal sympathetic nerve activity. Renal nerve activity interacts with the prevailing intrarenal pressure to modulate the release of renin.     

Renal injury caused by intrarenal injection of phenol increases afferent and efferent renal sympathetic nerve activity

Intrarenal injection of phenol in rats causes a persistent elevation in blood pressure (BP) and in norepinephrine (NE) secretion from the posterior hypothalamus (PH), and downregulation of neuronal nitric oxide synthase (nNOS) and interleukin-1beta (IL-1beta) in the PH. These studies suggest that afferent impulses from the kidney to the brain may be responsible for hypertension associated with renal injury. Downregulation of nNOS and IL-1beta, two modulators of sympathetic nervous system (SNS) activity may mediate this activation. In this study we measured the effects of intrarenal phenol injection on peripheral SNS activity by direct renal nerve recording, plasma NE, nNOS, and IL-1beta abundance in the brain. We also determined whether renal denervation or administration of clonidine prevented these effects of phenol. Acutely, the phenol injection increased both afferent and efferent renal sympathetic nerve activity, decreased urinary sodium excretion, and increased plasma NE. Three weeks after the phenol injection, BP and plasma NE remained elevated. Renal denervation and pretreatment with clonidine prevented the increase in BP and plasma NE caused by phenol. Chronic renal injury caused by phenol was associated with decreased abundance of IL-1beta and nNOS in the PH. These studies have shown that a renal injury caused by phenol injection increases BP and central as well as peripheral SNS activity, which persist long after the injury. Renal denervation and antiadrenergic drugs abolish the effects of phenol on BP and plasma NE. Because NO and IL-1beta modulate SNS activity, the stimulatory action of phenol on the SNS could be mediated by downregulation of nNOS and IL-1beta in the brain.     

特异性环氧合酶-2抑制剂对肾大部切除鼠进行性肾损害的保护作用

目的　探讨特异性环氧合酶 2 (COX 2 )抑制剂罗非昔布 (rofecoxib)延缓肾大部切除大鼠进行性肾损害的机制。方法　将大鼠随机分为假手术组、肾大部切除组 (SNX)、罗非昔布组、吲哚美辛组、氯沙坦组、罗非昔布与氯沙坦合用组 ,每组 6只。 6周后检测大鼠血压、尿蛋白及尿血栓素B2(TXB2 )的排泄量 ,观察肾组织病理改变 ,检测肾皮质血管紧张素Ⅱ (AngⅡ )浓度 ,应用免疫组化的方法检测纤维连接蛋白 (FN)的表达 ,逆转录 聚合酶链反应 (RT PCR)法检测转化生长因子 βⅠ型受体(TβRⅠ )及Ⅱ型受体 (TβRⅡ )的mRNA表达 ,免疫印迹法检测肾皮质COX 2、COX 1、纤溶酶原激活物抑制剂 1 (PAI 1 )及血管紧张素 1型受体 (AT1 )的表达。结果　与假手术组相比 ,SNX组大鼠尿蛋白及肾皮质COX 2的表达与尿TXB2 排泄明显增多 ,COX 1表达无明显变化 ;系统血压及AngⅡ浓度明显增高 ,肾皮质TβRⅠ及TβRⅡ的mRNA及PAI 1和AT1的表达显著上调 ,肾小球硬化指数及小管间质损伤指数增高。罗非昔布能明显减轻蛋白尿 (P <0 0 5)、减轻肾小球硬化指数及肾小管间质损伤指数(P <0 0 5) ,肾皮质TβRⅠ、TβRⅡ和PAI 1的表达较SNX组分别下调 36 44%、45 0 2 %和 31 1 6 % ,与氯沙坦作用相当。吲哚美辛组大鼠尿蛋白排泄及肾小球硬化指数较     

Neurovascular decompression of the rostral ventrolateral medulla decreases blood pressure and sympathetic nerve activity in patients with refractory hypertension

Recently, the authors experienced four patients who had refractory hypertension and neurovascular compression of the rostral ventrolateral medulla (RVLM). One of them, a 49-year-old woman, had undergone continuous intravenous drip injections of calcium channel blockers and β-blockers for more than 3 years because of severe and refractory hypertension. The patients had undergone microvascular decompression (MVD) of the RVLM, and the changes in blood pressure (BP) and sympathetic nerve activities were recorded. In these patients, BP decreased to the normal range without any antihypertensive drugs 2 to 3 months after MVD. The tibial sympathetic nerve activities under resting and stress conditions significantly decreased, and plasma levels of norepinephrine, urinary levels of adrenaline, and plasma renin activity were also significantly decreased after MVD of RVLM. In some patients with refractory hypertension, arterial compression of the RVLM enhances sympathetic nerve activity and renin-angiotensin system to thereby increase BP. In these patients, the operative decompression of the RVLM could lower BP via restoration of sympathetic nerve activities and the renin-angiotensin system.     

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)     

Renal denervation inhibits hypothalamo-sympathetic nerve system in normotensive and hypertensive rats

The role of the renal nerve in influencing the hypothalamo-sympathetic nerve system to regulate the cardiovascular system was studied in normotensive Wistar and spontaneously hypertensive rats (SHR). Renal denervation attenuated pressor and sympathetic nerve responses to electrical stimulation of the hypothalamus without lowering the basal blood pressure at 48 hours after denervated operation. These findings suggest that renal denervation could inhibit the hypothalamo-sympathetic nerve system in normotensive rats. The development of hypertension in SHR was completely inhibited by renal denervation during 2 weeks of observation (from 7 to 9 weeks of age) without increasing water intake and urine volume. Pressor responses to intravenous injection of norepinephrine were not affected by renal denervation. The results show that the antihypertensive effect of renal denervation was not due to the changing of vascular reactivity. Pressor and sympathetic nerve responses to hypothalamic stimulation were strongly diminished in renal denervated rats. These results suggest that renal denervation strongly inhibited they hypothalamo-sympathetic nerve system. It is also suggested that the renal afferent nerve may facilitate the hypothalamo-sympathetic nerve system in regulating blood pressure and that this facilitation may contribute to the development of hypertension in SHR.     

Brain renin-angiotensin system and ouabain-induced sympathetic hyperactivity and hypertension in Wistar rats.

In Dahl salt-sensitive rats on a high salt diet or normotensive rats with chronic central infusion of sodium, increased brain "ouabain" results in sympathetic hyperactivity and hypertension, possibly by activating the brain renin-angiotensin system. In the present study, we tested whether the hypertension caused by exogenous ouabain also depends on activation of brain renin-angiotensin system. In Wistar rats, ouabain (50 micrograms/d) was infused subcutaneously for 14 days with the use of osmotic minipumps. Concomitantly, in one group, the angiotensin II type 1 receptor blocker losartan (1 mg/kg per day) was infused intracerebroventricularly. On day 15, mean arterial pressure, heart rate, central venous pressure, and renal sympathetic nerve activity were recorded in conscious rats at rest and in response to air-jet stress, intracerebroventricular injection of the alpha(2)-agonist guanabenz (25 and 75 micrograms) or angiotensin II (30 ng), acute volume expansion, and ramp changes of blood pressure by +/-50 mm Hg with phenylephrine and nitroprusside. Compared with control rats, in rats treated with ouabain, resting mean arterial pressure was significantly increased (111+/-4 versus 93+/-3 mm Hg; P<0.05), and increases or decreases in mean arterial pressure, heart rate, and renal sympathetic nerve activity in response to air stress or guanabenz were enhanced significantly. These effects of ouabain were prevented when losartan was given concomitantly. Maximal slopes of arterial baroreflex control of renal sympathetic nerve activity and heart rate tended to be decreased in ouabain-treated versus control rats and were significantly increased in ouabain-treated rats with versus without losartan. No differences in cardiopulmonary baroreflex function were detected. It seems that by day 14 to 15, the central effect of ouabain on baroreflex control prevails over its peripheral sensitizing effect on baroreceptors, leading to a tendency of desensitization. These results indicate that chronic administration of ouabain activates the brain renin-angiotensin system, resulting in decreased sympathoinhibition and increased sympathoexcitation, impairment of baroreflex function, and hypertension.     

Unilateral Catheter-based Renal Sympathetic Denervation in Resistant Arterial Hypertension Shows No Blood Pressure-lowering Effect

A 68-year-old woman with resistant essential arterial hypertension despite the regular use of four antihypertensive drugs was referred to the catheter-based renal sympathetic denervation. Due to the complicated anatomy, insertion of the guiding catheter into the left renal artery was not stable. Thus, renal denervation of only the right renal artery was performed. Before and after renal denervation, the patient’s blood pressure was monitored by home blood pressure (BP) telemonitoring. The average 7-day home BP telemonitoring values before and 1, 2, and 3 months after denervation were 187.1/124.1, 193.3/123.1, 198.3/129.6, and 195.2/128.0 mm Hg. After unilateral renal denervation, no BP decrease occurred. This unique case suggests that unilateral catheter-based renal sympathetic denervation in resistant arterial hypertension shows no BP-lowering effect. Therefore, when treating resistant hypertension by catheter-based renal denervation, it seems advisable to try always to perform an effective bilateral procedure.     

Renal vascular adjustments to partial renal venous obstruction in dog kidney

Blood flow studies were conducted in neurolept anesthetized dogs to characterize the involvement of renal nerves in ipsilateral renal vasoconstriction seen during acute elevation of renal venous pressure above 30 mm Hg. Renal blood flow was measured electromagnetically. The vasoconstrictor response was almost abolished by acute surgical denervation of the kidney, since renal vascular conductance remained unchanged during renal venous pressure elevation from 30-60 mm Hg. However, following additional alpha-adrenoceptor blockade or chronic renal denervation, renal vascular conductance increased progressively during renal venous pressure elevation to 60 mm Hg. The effect of acute decapsulation of kidney was studied in another group of dogs. Decapsulation induced a vasoconstriction. The decrease in renal vascular conductance observed during renal venous pressure elevation was unaffected by acute surgical denervation of decapsulated kidney, but was almost abolished following additional alpha-adrenoceptor blockade or chronic denervation. In decapsulated chronically denervated kidney, the increase in renal vascular conductance during renal venous pressure elevation to 60 mm Hg was still present but considerably attenuated as compared with the chronically denervated kidney with intact capsule. The renin-angiotensin system did not participate in acute vascular adjustments to renal venous stasis in intact kidney or in decapsulated acutely surgically denervated kidney. The data favor the view that neurogenic and myogenic mechanisms significantly influence the vasoconstrictor response to renal venous pressure elevation in dog kidney. The neurogenic contribution to the vasoconstrictor response comprises intrarenal and extrarenal vasoconstrictor mechanisms evoked reflexively by renal venous pressure elevation, and the myogenic contribution to the vasoconstrictor response comprises opposing vasodilator mechanisms due to increase in renal interstitial tissue pressure during renal venous pressure elevation.     

Effects of renal sympathetic denervation on blood pressure, sleep apnea course, and glycemic control in patients with resistant hypertension and sleep apnea

Percutaneous renal sympathetic denervation by radiofrequency energy has been reported to reduce blood pressure (BP) by the reduction of renal sympathetic efferent and afferent signaling. We evaluated the effects of this procedure on BP and sleep apnea severity in patients with resistant hypertension and sleep apnea. We studied 10 patients with refractory hypertension and sleep apnea (7 men and 3 women; median age: 49.5 years) who underwent renal denervation and completed 3-month and 6-month follow-up evaluations, including polysomnography and selected blood chemistries, and BP measurements. Antihypertensive regimens were not changed during the 6 months of follow-up. Three and 6 months after the denervation, decreases in office systolic and diastolic BPs were observed (median: -34/-13 mm Hg for systolic and diastolic BPs at 6 months; both P<0.01). Significant decreases were also observed in plasma glucose concentration 2 hours after glucose administration (median: 7.0 versus 6.4 mmol/L; P=0.05) and in hemoglobin A1C level (median: 6.1% versus 5.6%; P<0.05) at 6 months, as well as a decrease in apnea-hypopnea index at 6 months after renal denervation (median: 16.3 versus 4.5 events per hour; P=0.059). In conclusion, catheter-based renal sympathetic denervation lowered BP in patients with refractory hypertension and obstructive sleep apnea, which was accompanied by improvement of sleep apnea severity. Interestingly, there are also accompanying improvements in glucose tolerance. Renal sympathetic denervation may conceivably be a potentially useful option for patients with comorbid refractory hypertension, glucose intolerance, and obstructive sleep apnea, although further studies are needed to confirm these proof-of-concept data.