Changes in B-Group Vitamin Status in Adenine-Induced Chronic Renal Failure Rats

The antihypertensive effect of Brand's Essence of Chicken (BEC), a popular chicken extract used as a traditional health food, was examined with stroke-prone spontaneously hypertensive rats (SHRSPs). The animals were maintained from 6 to 25 weeks of age on drinking water with or without BEC. The BEC-fed group showed a significant reduction in the development of hypertension when compared with the control animals. The levels of blood urea nitrogen and plasma creatinine in the BEC-fed group were significantly lower than those in the control group, suggesting that the renal glomerular function had been improved by the daily administration of BEC. It thus seems likely that BEC would be useful as a prophylactic treatment against the development of hypertension and renal injury.     

Contribution of renal innervation to hypertension in rat autosomal dominant polycystic kidney disease

The kidney has both afferent (sensory) and efferent (sympathetic) nerves that can influence renal function. Renal innervation has been shown to play a role in the pathogenesis of many forms of hypertension. Hypertension and flank pain are common clinical manifestations of autosomal dominant (AD) polycystic kidney disease (PKD). We hypothesize that renal innervation contributes to the hypertension and progression of cystic change in rodent PKD. In the present study, the contribution of renal innervation to hypertension and progression of renal histopathology and dysfunction was assessed in male Han:SPRD-Cy/+ rats with ADPKD. At 4 weeks of age, male offspring from crosses of heterozygotes (Cy/+) were randomized into either 1) bilateral surgical renal denervation, 2) surgical sham denervation control, or 3) nonoperated control groups. A midline laparotomy was performed to allow the renal denervation (i.e., physical stripping of the nerves and painting the artery with phenol/alcohol). Blood pressure (tail cuff method), renal function (BUN) and histology were assessed at 8 weeks of age. Bilateral renal denervation reduced the cystic kidney size, cyst volume density, systolic blood pressure, and improved renal function (BUN) as compared with nonoperated controls. Operated control cystic rats had kidney weights, cyst volume densities, systolic blood pressures, and plasma BUN levels that were intermediate between those in the denervated animals and the nonoperated controls. The denervated group had a reduced systolic blood pressure compared with the operated control animals, indicating that the renal innervations was a major contributor to the hypertension in this model of ADPKD. Renal denervation was efficacious in reducing some pathology, including hypertension, renal enlargement, and cystic pathology. However, sham operation also affected the cystic disease but to a lesser extent. We hypothesize that the amelioration of hypertension in Cy/+ rats was due to the effects of renal denervation on the renin angiotensin system.     

Plasma active and acid-activatable renin during the development of one-kidney, one-clip and two-kidney, one-clip hypertension in the rabbit.

Systolic blood pressure in the central ear artery of eight rabbits increased by 21 mmHg (1 mmHg = 133.32 Pa) over 40 days following renal artery clipping and contralateral nephrectomy (one-kidney, one-clip). Plasma active and acid-activatable (pH 2.8) renin did not change significantly. Similar data were obtained from a group of 12 rabbits following renal artery clipping alone (two-kidney, one-clip) except that blood pressure in this group increased for 26 days but then declined until 40 days. Two animals with one-kidney, one-clip hypertension and three rabbits with two-kidney, one-clip hypertension had large increases in plasma active and inactive renin levels, which followed a more exaggerated rise in blood pressure than in the previous two groups. Forty days after unilateral renal artery clipping, the unclipped kidney was removed in 10 animals with two-kidney, one-clip hypertension. A further increase in blood pressure (+29%) occurred in seven of the animals but no change in plasma active or inactive renin. Results were compared with two groups of control animals, a unilateral nephrectomy group and a laparotomy group. None of the surgical procedures used produced a consistent pattern of change in the relative amounts of active and inactive renin in plasma. No marked changes in sodium, potassium, or water balance occurred in any group of animals.     

The effect of chronic alcohol inhalation on blood pressure and the pressor response to noradrenaline and the thromboxane-mimic U46619

Rats were exposed to alcohol vapor for 6 days and the mean blood ethanol concentration (BEC) was obtained for each subject. Blood pressure and its reactivity to noradrenaline and a thromboxane-mimic U46619 were directly measured on day 6 via a catheter implanted in the tail artery of normal and ethanol-treated animals. The mean BEC for each subject correlated with mean arterial blood pressure (MAP); an increase in BEC was associated with a decrease in MAP (p less than 0.02). The mean MAP of subjects with BEC less than 168 mg% was 8% higher than normal (not significant), whereas, the mean MAP of subjects with BEC greater than 182 mg% decreased 27 +/- 4% (p less than 0.01). Conversely, the pressor response to U46619 was markedly enhanced (p less than 0.005) in rats with mean BEC greater than 182 mg% at all doses investigated (12.5-3200 ng per rat). Increases in the pressor response to noradrenaline in ethanol-treated rats were significant only when maximally stimulated by 400 and 800 ng doses (p less than 0.03). A 3-fold increase in sensitivity for U46619 was seen in subjects with high mean BEC, however, sensitivity for noradrenaline did not significantly change. Vasoreactivity was not effected in rats with mean BEC less than 168 mg%. These data demonstrate that a moderate mean BEC for 6 days induces a tendency towards a mild hypertension, whereas, high mean BEC induces marked hypotension which is associated with hyperreactivity. Long-term exposure to high blood ethanol concentrations may predispose the alcohol-dependent rats to hypertensive disease and vasospastic disorders, at least partially, as a result of enhanced sensitivity to prostaglandins such as thromboxane.     

Correlation of the fibrinogen level with blood pressure and plasma renin activity in rats with early Goldblatt hypertension

Goldblatt hypertension was induced in rats by constricting the renal artery on one side. In one group of animals the contralateral kidney remained untouched (two-kidney hypertension), while in the other it was removed (one-kidney hypertension). In the two-kidney hypertension group, renin activity was higher than in the control animals, the fibrinogen was normal both in arterial and venous blood while in one-kidney hypertension the PRA was normal, but the fibrinogen was increased. A close significant correlation could be demonstrated between blood pressure and fibrinogen.     

Mizoribine Ameliorates Renal Injury and Hypertension along with the Attenuation of Renal Caspase-1 Expression in Aldosterone-Salt-Treated Rats

Aldosterone-salt treatment induces not only hypertension but also extensive inflammation that contributes to fibrosis in the rat kidney. However, the mechanism underlying aldosterone-salt-induced renal inflammation remains unclear. Pyroptosis has recently been identified as a new type of cell death that is accompanied by the activation of inflammatory cytokines. We hypothesized that aldosterone-salt treatment could induce inflammation through pyroptosis and that mizoribine, an effective immunosuppressant, would ameliorate the renal inflammation that would otherwise cause renal fibrosis. Ten days after recovery from left uninephrectomy, rats were given drinking water with 1% sodium chloride. The animals were divided into three groups (n = 7 per group): (1) vehicle infusion group, (2) aldosterone infusion group, or (3) aldosterone infusion plus oral mizoribine group. Aldosterone-salt treatment increased the expression of the nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3 and caspase-1, and also increased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells. However, the oral administration of mizoribine attenuated these alterations. Furthermore, mizoribine inhibited hypertension and renal fibrosis, and also attenuated the aldosterone-induced expression of serum/glucocorticoid-regulated kinase and α epithelial sodium channel. These results suggest that caspase-1 activation plays an important role in the development of inflammation induced by aldosterone-salt treatment and that it functions as an anti-inflammatory strategy that protects against renal injury and hypertension.     

Interactions between 11beta-hydroxysteroid dehydrogenase and COX-2 in kidney

The syndrome of apparent mineralocorticoid excess (SAME) is an autosomal recessive form of salt-sensitive hypertension caused by deficiency of the kidney type 2 11beta-hydroxysteroid dehydrogenase (11betaHSD2). In this disorder, cortisol is not inactivated by 11betaHSD2, occupies mineralocorticoid receptors (MRs), and causes excessive sodium retention and hypertension. In renal medulla, prostaglandins derived from cyclooxygenase-2 (COX-2) stimulate sodium and water excretion, and renal medullary COX-2 expression increases after mineralocorticoid administration. We investigated whether medullary COX-2 also increases in rats with 11betaHSD2 inhibition and examined its possible role in the development of hypertension. 11betaHSD2 inhibition increased medullary and decreased cortical COX-2 expression in adult rats and induced high blood pressure in high-salt-treated rats. COX-2 inhibition had no effect on blood pressure in control animals but further increased blood pressure in high-salt-treated rats with 11betaHSD2 inhibition. COX-1 inhibition had no effect on blood pressure in either control or experimental animals. 11betaHSD2 inhibition also led to medullary COX-2 increase and cortical COX-2 decrease in weaning rats, primarily through activation of MRs. In the suckling rats, medullary COX-2 expression was very low, consistent with a urinary concentrating defect. 11betaHSD2 inhibition had no effect on either cortical or medullary COX-2 expression in the suckling rats, consistent with low levels of circulating corticosterone in these animals. These data indicate that COX-2 plays a modulating role in the development of hypertension due to 11betaHSD2 deficiency and that 11betaHSD2 regulates renal COX-2 expression by preventing glucocorticoid access to MRs during postnatal development.     

Influence of age on saline hypertension in subtotal nephrectomized rats

In uninephrectomised immature and adult male rats 34% renal tissue was removed from the remaining kidney and after 60-days exposure to saline treatment (0.17 mol/l NaCl solution as only drinking fluid) the mean arterial blood pressure, plasma urea concentration, plasma and extracellular fluid volumes were estimated. In comparison with water drinking uninephrectomised age-matched controls it has been found that: in both age groups, the loss of tissue from the remaining kidney was fully replaced by compensatory growth of the renal stump, plasma urea concentration remained unchanged in animals operated on when adult, but increased in animals operated on when immature, the interstitial fluid volume increased in both age groups--the plasma volume as well as blood pressure remained unchanged in animals treated when adult, but increased in animals treated when immature. It is concluded that under conditions of elevated salt intake the loss of renal mass in immature rats was compensated by growth of tissue with a lower excretory ability than in adult ones, this being responsible for the development of hypertension in the younger group.     

Effects of niacin-bound chromium, Maitake mushroom fraction SX and (–)-hydroxycitric acid on the metabolic syndrome in aged diabetic Zucker fatty rats

Previous studies in our laboratories have demonstrated that niacin-bound chromium (NBC), Maitake mushroom and (–)-hydroxycitric acid (HCA-SX) can ameliorate hypertension, dyslipidemias and diabetes mellitus, and therefore may be useful in weight management. In the present study, we used aged, diabetic Zucker fatty rats (ZFR) (70–75 weeks) in order to determine whether NBC, fraction SX of Maitake mushroom (MSX) and 60% (–)-hydroxycitric acid (HCA-SX) from Garcinia cambogia, alone or in combination, can affect certain aspects of the metabolic syndrome. Syndrome X or metabolic syndrome has been described as a concurrence of disturbed glucose and insulin metabolism, overweight and abdominal fat distribution, mild dyslipidemia, and hypertension, which are associated with subsequent development of type 2 diabetes mellitus and cardiovascular disease. Four groups of eight ZFR were gavaged daily with different supplements. For the initial three weeks, the control group of ZFR received only water, the second group received NBC 40 mcg elemental chromium/day, the third group received MSX 100 mg/day and the last group received HCA-SX 200 mg/day. During weeks 4–6, the doses of each treatment were doubled. The control animals lost approximately 50 g body weight (BW) per rat over 6 weeks of treatment, which is characteristic of these animals in declining health. In contrast, eight ZFR receiving NBC lost approximately 9 g BW per rat, while rats consuming MSX lost 16 g BW per rat. However, ZFR receiving HCA-SX simulated the pattern in the control group because these animals lost approximately 46 g BW per rat. The wide individual variations resulted in a lack of statistical significance among groups. Nevertheless, 75% of the ZFR in the control group lost more than 50 g BW over the 6 weeks duration, whereas none of the ZFR receiving NBC, 25% of the ZFR receiving MSX and 57% of the ZFR receiving HCA-SX lost over 50 g BW over the 6 weeks of the study. ZFR in all 3 treatment groups showed significantly lower blood pressures as compared to control, which seemed to be dose related. The general trend was for renal and liver blood parameters, hepatic and renal lipid peroxidation and DNA fragmentation to improve due to the supplementation of these natural products. Treatment of animals with a combination of these three novel supplements resulted in a lower SBP and maintenance of BW compared to control animals. These results demonstrate that elderly diabetics and even aging individuals might benefit from a similar regimen.     

Semiquantitative histochemical investigation of lysosomal enzyme activities in the aortic endothelial cells of rats with renal hypertension

To obtain information about changes in lysosomal enzyme activities in the aortic endothelial cells in arterial hypertension, semi-quantitative histochemical investigations of acid phosphatase (Ac-Pase) and N-acetyl-beta-glucosaminidase (NAGase) activities in the aorta of rats with renal hypertension were performed on "H?utchen" monolayer preparations. The aortic endothelial cells in renal hypertensive animals showed increased Ac-Pase and NAGase activities compared with those in control normotensive rats and tended to increase with advancing age. These results, like our previous data from spontaneously hypertensive rats (SHR), indicated that degeneration of endothelial cells, expressed by increased lysosomal enzyme activity, was accelerated by hypertension, and the possible participation of genetic factors in the activation of these enzymes in SHR was ruled out. Increased lysosomal enzyme activity may be involved in the development of other hypertensive vascular changes.     

依那普利联合氯沙坦治疗老年肾性高血压的临床观察

目的:探讨依那普利联合氯沙坦治疗老年肾性高血压的效果.方法:选取2008年2月～2011年10月我院收治的肾性高血压患者70例,按随机数字表法分为观察组和对照组,每组35例.对照组给予依那普利20mg,每天2次;观察组给予依那普利10mg,每天2次;氯沙坦50mg,每天1次.观察两组血压、肾功能指标变化及不良反应.结果:观察组总有效率为95.0％(38/35),对照组为75.0％(30/35),差异有统计学意义(P＜0.05);治疗后两组血压(DBP、SBP)和肾功能(SCr、BUN、mAlb)指标均明显改善(P＜0.05),观察组较对照组改善更为明显(P＜0.05);观察组不良反应发生为17.14％(6/35),对照组为14.29％(5/35),差异无统计学意义(P＞0.05).结论:依那普利联合氯沙坦治疗老年肾性高血压能更有效改善血压和肾功能,安全性高.     

Effect of valsartan on angiotensin II- and vasopressin-degrading activities in the kidney of normotensive and hypertensive rats.

Valsartan, a selective antagonist of angiotensin II at the AT(1) receptor subtype, is an efficacious, orally active, blood pressure-lowering agent used in hypertensive patients. Given that aminopeptidases (APs) play a major role in the metabolism of local peptides involved in blood pressure control, studying them helped us to understand cardiovascular control. We studied the effect of valsartan on angiotensin II- (GluAP) and vasopressin- (CysAP) degrading activities in the kidney in the rat model of renovascular hypertension, Goldblatt two-kidney one-clip. GluAP and CysAP in renal cortex and medulla exhibited different responses to hypertension and valsartan treatment. In the renal cortex, GluAP decreased in clipped and non-clipped kidneys of hypertensive animals. However, while hypertension did not affect GluAP in the clipped kidney medulla, the non-clipped kidney exhibited an increase in soluble and a decrease in membrane-bound activity. Valsartan decreased soluble GluAP in the medulla of normotensive and hypertensive animals. In the renal cortex, CysAP activity was mainly downregulated following hypertension. Valsartan decreased soluble CysAP activity in sham-operated, but not in hypertensive animals. The renal medulla showed a significant valsartan-related decreased activity in clipped and non-clipped kidneys of both sham-operated and hypertensive animals. These results suggest a functional relationship between the AT(1) receptor and vasopressin-degrading activity.     

Oxidative stress, nitric oxide production, and renal sodium handling in leptin-induced hypertension

Chronic hyperleptinemia induces arterial hypertension in experimental animals and may contribute to the development of hypertension in obese humans; however, the mechanism of hypertensive effect of leptin is not completely elucidated. We investigated the effect of leptin on whole-body oxidative stress, nitric oxide production, and renal sodium handling. The study was performed on male Wistar rats divided into 3 groups: 1) control, fed standard chow ad libitum, 2) leptin-treated group, receiving leptin injections (0.25 mg/kg twice daily s.c. for 7 days), 3) pair-fed group, in which food intake was adjusted to the leptin group. Leptin caused 30.5% increase in systolic blood pressure. Plasma concentration and urinary excretion of 8-isoprostanes in animals receiving leptin was 46.4% and 49.2% higher, respectively. The level of lipid peroxidation products, malonyldialdehyde + 4-hydroxyalkenals, increased by 52.5% in the renal cortex and by 48.4% in the renal medulla following leptin treatment, whereas aconitase activity decreased in these regions of the kidney by 45.3% and 39.2%, respectively. Urinary excretion of nitric oxide metabolites (NOx) was 55.0% lower, and fractional excretion of NOx was 55.8% lower in the leptin-treated group. Urinary excretion of cGMP decreased in leptin-treated rats by 26.3%. Following leptin treatment, absolute and fractional sodium excretion decreased by 35.0% and 41.2%, respectively. These results indicate that hyperleptinemia induces systemic and intrarenal oxidative stress, decreases the amount of bioactive NO possibly due to its degradation by reactive oxygen species, and causes renal sodium retention by stimulating tubular sodium reabsorption. NO deficiency and abnormal renal Na+ handling may contribute to leptin-induced hypertension.     

Renal hyperemia in portal hypertension is not mediated by gastrointestinal peptides

The objectives of this study were to characterize the time course of development of the renal hyperemia induced by chronic portal vein stenosis (PVS) in the rat, and to assess the possibility that vasoactive blood-borne gastrointestinal peptides mediate the renal hyperemia in established portal hypertension. Blood flow to the kidneys was measured with radioactive microspheres over a ten day time course. On day 2, no difference in renal blood flow (RBF) was observed in PVS rats as compared with controls. However, by day 4, RBF significantly increased by 35% in PVS vs. control animals. On day 6, the renal hyperemia in PVS rats reached a maximal value that was 42% higher than controls. A steady state hyperemia (approximately 40%) was maintained thereafter. Radioimmunoassay of plasma from control and established portal hypertensive rats (10 days samples) revealed that vasoactive intestinal polypeptide, substance P, cholecystokinin, gastrin, neurotensin, pancreatic polypeptide, beta-endorphin and peptide histidine-isoleucine amide are not elevated in arterial plasma of portal hypertensive rats. These data suggest that the renal hyperemia induced by chronic portal vein stenosis is apparent within 4 days of the onset of a hypertensive state and attains a steady state by day 8. Furthermore, at least eight blood-borne gastrointestinal peptides are not directly involved in the renal hyperemia associated with chronic portal hypertension.     

硝苯地平联合缬沙坦治疗老年原发性高血压疗效分析

目的:探讨硝苯地平缓释片联合缬沙坦治疗老年原发性高血压的临床疗效。方法:将180例患者随机分入对照组与观察组,给予对照组86例患者硝苯地平缓释片口服降压;观察组94例患者接受硝苯地平缓释片联合缬沙坦治疗,比较两组患者治疗8周后血压、心率、脉压、肾功、尿酸、血钾及尿微量白蛋白的变化。结果:治疗后观察组患者收缩压、舒张压、脉压及心率均显著降低,治疗总有效率高于对照组,两组比较差异有统计学意义(P<0.01);观察组尿酸、尿微量白蛋白显著优于对照组(P<0.01),两组肾功、血钾比较差异无统计学意义(P>0.05)。结论:硝苯地平缓释片联合缬沙坦治疗老年原发性高血压,降压平稳,同时可显著降低尿酸及尿微量白蛋白,改善肾功能。     

Norepinephrine turnover in the heart and blood vessels of rats subjected to bilateral renal infarction

The total norepinephrine (NE) content, the uptake of [3H]NE, the turnover rate and the synthesis rate of the neurotransmitter at the heart and blood vessels have been studied during the development of hypertension in rats subjected to bilateral renal infarction. Normal and sham-operated rats were used as controls. Fifty percent of the rats with renal infarction became hypertensive. The weight of the hearts and blood vessels of the experimental animals was significantly increased 15 days after renal infarction. Changes were greater in hypertensive animals. NE concentration in the heart was slightly decreased without achieving statistical significance, while total NE content was unchanged. In the artery wall NE concentration was significantly decreased in normotensive and hypertensive operated rats. [3H]NE uptake in the heart and blood vessels was similar in experimental and control animals. In relation to NE turnover, in both the heart and blood vessels, normal and sham-operated animals behaved as one population while normotensive and hypertensive rats behaved as another population. The rate constant of NE turnover was increased in both tissues of operated experimental animals without achieving statistical significance in the case of the heart. NE synthesis rate was unchanged in the cardiac muscle but was significantly increased in the blood vessels of operated animals. Present data indicate that results describing NE dynamics in the heart cannot be extrapolated for the blood vessels level; on the other hand changes in the neurotransmitter do not seem to be related to the development of high blood pressure after renal infarction in the rat.     

High salt intake attenuates the development of hypertension in two-kidney, one-clip Goldblatt rats.

Effects of high salt intake on the early onset of hypertension were examined in two-kidney, one-clip rats. They were divided into high salt and control groups which were supplied with 1.0% NaCl and tap water, respectively, as a drinking solution for 12 days after clipping the left renal artery. The high salt group showed a lower plasma renin concentration and a higher plasma atrial natriuretic peptide (ANP) along with an attenuation of the magnitude of early hypertension, as compared with the control group. A significant positive correlation between blood pressure and plasma renin concentration and an inverse correlation between plasma renin concentration and ANP were shown. Cortical renal renin content was comparable between the two groups. In another two groups of sham-clipped rats, the high salt group did not differ from the tap water-drinking group in any of the parameters examined, except that ANP was significantly higher. These results demonstrate that high salt intake attenuates the developmental phase of hypertension in two-kidney, one-clip rats by increasing the ANP and suppressing the release of renin.     

Glomerular profile numerical density per area and mean glomerular volume in rats submitted to nitric oxide synthase blockade

Rats submitted to chronic inhibition of nitric oxide synthase (NOS) have developed systemic hypertension and consequent renal injury. The present study aims to determine glomerular quantitative changes due to NOS inhibition in rats. Adults and normotensive Wistar rats were separated into control and L-NAME groups (each group n=10). The animals received water and food ad libitum, while L-NAME rats received NG-Nitro-L-Arginine methyl Ester hydrochloride to inhibit NOS (50mg/kg/day) in drinking water during 40 days. After that period the rats were sacrificed, the kidneys were removed, measured, and prepared for histological and stereological analyses. The glomerular density per area [NA(glom)] and the mean glomerular volume [v] were determined per animal in 15 random fields. In L-NAME rat the blood pressure was 76% higher than the respective control group with the same age. Glomeruli had global or segmental glomerular sclerosis; some glomeruli only presented an atrophic structure. The renal volume was not different between control and L-NAME rats (p>0.05). However, L-NAME rats had the NA(glom) 33% smaller than the control rats (p=0.0001) and, concomitantly, L-NAME rats had the v (glom) 33% higher than the control ones (p=0.004). These results demonstrate morphological renal alterations caused by NOS inhibition and hypertension.     

Blood pressure in a hypertensive mouse model of SLE is not salt-sensitive

Systemic lupus erythematosus (SLE) is a risk factor for hypertension. Previously, we demonstrated that an established mouse model of SLE (female NZBWF1 mice) develops hypertension with renal inflammation and oxidative stress, both characteristics known as contributing mechanisms to the development of salt-sensitive hypertension. On the basis of this model, we hypothesized that blood pressure in SLE mice would be salt-sensitive. Thirty-week-old female SLE and control mice (NZW/LacJ) were fed 8% high-salt (HS) diet or normal diet (0.4% salt) for 4 wk. Plasma levels of double-stranded DNA (dsDNA) autoantibodies, a marker of SLE disease activity, were increased in SLE mice compared with controls (472 ± 148 vs. 57 ± 17 U/ml × 1,000, P < 0.001). HS did not alter dsDNA autoantibody levels in SLE or control mice. Mean arterial pressure was increased in SLE mice compared with controls (132 ± 3 vs. 118 ± 2 mmHg, P < 0.001) and was not significantly altered by the HS diet in either group. Similarly, albuminuria was higher in SLE mice compared with controls (10.7 ± 9.0 vs. 0.3 ± 0.1 mg/day) but was not significantly increased in SLE or control mice fed a HS diet. In summary, blood pressure during SLE is not salt-sensitive, and the HS diet did not adversely affect SLE disease activity or significantly augment albuminuria. These data suggest that renal inflammation and oxidative stress, characteristics common to both SLE and models of salt-sensitive hypertension, may have diverging mechanistic roles in the development of hypertension.     

Sympathetic activity in early renal posttransplantation hypertension in rats

The contribution of elevated sympathetic activity to the development of renal posttransplantation hypertension was investigated. F1 hybrids (F1H) from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were transplanted with either an SHR or an F1H kidney and bilaterally nephrectomized. Three weeks after transplantation, sympathetic activity was assessed by measuring adrenal tyrosine hydroxylase (TH) mRNA content and recording splanchnic nerve activity (SNA) in conscious animals. To investigate the dependence of arterial pressure on sympathetic activity, animals were treated with the alpha(2)-adrenoceptor agonist guanabenz intracerebroventricularly. Mean arterial pressure (MAP) was 143 +/- 4 mmHg in recipients of an SHR kidney (n = 15) versus 110 +/- 3 mmHg in recipients of an F1H kidney (n = 10; P < 0.001). Adrenal TH mRNA content was 1.93 +/- 0.15 fmol/microg total RNA in recipients of an SHR kidney versus 1.96 +/- 0.17 fmol/microg total RNA in recipients of an F1H kidney (not significant). SNA did not differ significantly between recipients of an SHR kidney (n = 8) and recipients of an F1H kidney (n = 7) in terms of frequency and amplitude of synchronized nerve discharges. In response to cumulative intracerebroventricular administration of 10 and 20 microg guanabenz, SNA fell to 51 +/- 5% of control in recipients of an SHR kidney versus 44 +/- 6% of control in recipients of an F1H kidney (not significant) accompanied by a slight fall in MAP in either group. The results suggest that elevated sympathetic activity is not a major contributor to the development of renal posttransplantation hypertension.