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PubMed1992

Dietary sodium restriction and the development of two-kidney, one-clip hypertension in young versus adult rats.

To determine the effects of moderate versus severe dietary sodium restriction on the development of 2-kidney, 1-clip (2K,1C) hypertension, young male Wistar rats were placed on diets containing 9, 26, or 101 (control) mumol sodium/g food. Three days later, a solid silver clip (i.d. 0.20 mm) was placed on the left renal artery and diets were continued up to 6 weeks. Adult rats received a 0.25-mm clip. In young clipped rats receiving the 101 mumol/g diet, blood pressure (BP), plasma renin activity (PRA), and BP response to captopril were increased as early as 1 week after clipping and increased further over time. Moderate sodium restriction (26 mumol sodium/g) led to only a slight delay in the development of hypertension; the levels of BP and PRA, the BP response to captopril, and the extent of cardiac hypertrophy achieved by 6 weeks were not different between the 2K, 1C rats receiving 26 or 101 mumol sodium/g. Sodium restriction to 9 mumol/g decreased rate of growth and completely prevented the rise in BP and in left ventricular weight. At 3 and 6 weeks the severely sodium-restricted rats had significantly higher PRA levels than the 2K, 1C control group. However, the BP response to captopril was attenuated relative to the other hypertensive groups. In adult rats, this level of sodium restriction had a small, but significant effect on body weight, but still prevented the increase in BP and in left ventricular weight. In conclusion, dietary sodium restriction can prevent the development of 2K,1C hypertension in both young and adult rats, but only if the restriction is severe. This effect may relate to a marked reduction in the pressor effectiveness of the renin-angiotensin system by low sodium intake per se or by associated metabolic or other changes.

Aging↗
PubMed1985

Surgical ligation clip artifacts on CT scans.

Surgical ligation clips of various materials were scanned in a water-filled phantom to determine what artifacts would be produced. Tantalum clips produced severe image degradation, while stainless steel clips produced less severe degradation. Minimal artifacts were observed with titanium clips. Clips molded from an absorbable polymeric material, polydioxanone, were visible on computed tomography (CT) scans and had the least effect on the CT image.

Humans↗
PubMed1993

Suppression by central AVP of prostaglandin E1 hyperthermia in one-kidney, one-clip Goldblatt hypertensive rats.

We have investigated the ability of the one-kidney, one-clip (1K,1C) hypertensive rat to develop a hyperthermic response to intracerebroventricular injection of prostaglandin (PG) E1. Accordingly, core temperature was monitored in response to PGE1 injections both preoperatively and on days 4, 8, 12, and 18 after either unilateral nephrectomy or the induction of hypertension due to nephrectomy plus renal artery clipping. Temperature responses to PGE1 were similar throughout each test day in normotensive, unilaterally nephrectomized control rats. In contrast, 1K,1C rats became hypertensive within 4 days of renal artery clipping, and at this time the hyperthermic response to PGE1 was virtually abolished. A reduced hyperthermic response was also seen at 8 and 12 days after clipping; by 18 days responses were again similar to controls. To determine whether central arginine vasopressin (AVP) was involved in the suppression of the hyperthermic response, we pretreated other hypertensive rats centrally with the V1-AVP antagonist [d(CH2)5Tyr(Me)]AVP before PGE1 injection. In 1K,1C animals thus treated, temperature responses 4-12 days after clipping were indistinguishable from those of similarly treated normotensive control rats. We suggest that the reduced hyperthermic responses to PGE1 seen in the 1K,1C rats during the initial development of hypertension may be due to activation of brain AVP pathways.

Alprostadil↗
PubMed2006

Angiotensin II-induced calcium signaling in the afferent arteriole from rats with two-kidney, one-clip hypertension.

The aim of this study was to investigate ANG II-induced Ca2+ signaling in freshly isolated afferent arterioles (AA) from two-kidney, one-clip hypertensive (2K1C) rats, which have an elevated plasma and renal ANG II level, and different perfusion pressure and vascular tone in the clipped and nonclipped kidney. The Ca2+ responses in vessels from 2K1C and control rats were similar in all groups (P>0.1). The intracellular Ca2+ (Cai2+) response in the afferent arteriole after 10(-8) M ANG II stimulation was 0.57+/-0.10, 0.50+/-0.07, 0.48+/-0.04, and 0.36+/-0.05 in the control, sham, nonclipped, and clipped kidney, respectively. These data were consistent with the finding of unchanged AT(1a)R mRNA levels in AAs from all groups. Although the absolute values were similar, the dose-response curves to ANG II were different. In the control, sham, and nonclipped kidney from 2K1C, the dose-response curve leveled off between 10(-8) and 10(-6) M ANG II. In the clipped kidney, the dose-response curve was linear, with a significantly increased response at 10(-6) M compared with 10(-8) M ANG II (P<0.05). Inhibition of cyclooxygenase-1 (COX-1) with indomethacin enhanced the ANG II response in the nonclipped (Delta0.30+/-0.09) and clipped (Delta0.30+/-0.09) kidneys from 2K1C (P<0.005), but not in control rats (Delta-0.02+/-0.11, P>0.8). Conclusively, the ANG II-induced Cai2+ response was reduced by COX-1-derived prostaglandins in 2K1C, in contrast to control animals, where the COX-1 inhibition had no effect. COX-2 inhibition with NS-398 did not increase the ANG II-mediated Cai2+ response in any of the groups.

Angiotensin II↗
PubMed1984

Glomerular prostaglandin formation in two-kidney, one-clip hypertensive rats.

In vitro prostaglandin (PG) and thromboxane B2 (TXB2) formation by isolated glomeruli from normotensive (N) and two-kidney, one-clip hypertensive (2K,1C) rats was determined. When calculated on the basis of glomerular protein content, PGE2, 6-keto-PGF1 alpha and TXB2 production of glomeruli from clipped kidneys was significantly greater than PG and TXB2 formation of glomeruli from the untouched kidneys. When PG and TXB2 formation was calculated per amount of glomeruli, only PGE2 formation was found to be significantly greater in clipped kidneys. No severe damage of glomerular structure was found in the kidneys when studied by light microscopy. In additional in vivo studies, the effect of the cyclooxygenase inhibitor indomethacin on blood pressure and glomerular filtration rate (GFR) was evaluated. Following indomethacin GFR in 7 of 13 clipped kidneys of 2K,1C rats decreased from 363 +/- 77 to 188 +/- 51 microliter/100 g body wt, whereas six kidneys developed anuria. No effect of cyclooxygenase inhibition on GFR was found in N rats and in untouched kidneys of 2K,1C rats. Mean arterial blood pressure in 2K,1C hypertension fell significantly, from 158 +/- 10 to 135 +/- 7 mmHg, after cyclooxygenase inhibition. No effect was seen in N rats. The data suggest that increased glomerular PG formation in the clipped kidneys of 2K,1C rats is involved in the pathogenesis of hypertension in this animal model.

Animals↗
PubMed1990

Differential Na fluxes with artificial and native fluids in clip models of volume expansion.

Earlier we demonstrated significant differences in proximal tubular Na transport inhibition during saline volume expansion (VE) depending on whether artificial (AF) or native harvested tubular fluid (HTF) was used. In the present experiments the shrinking-drop technique was used to measure volume flux (Jv) in the early- and late-clip models of VE with AF alternating with HTF. In early-clip rats, with AF, Jv (x 10(4) mm3.mm-2.s-1) during the nonexpanded period was 2.92 +/- 0.105; during subsequent VE, it was 2.20 +/- 0.180 and 1.97 +/- 0.149 with HTF (for the latter two P greater than 0.3). In late-clip rats they were 2.83 +/- 0.135, 1.99 +/- 0.157, and 1.50 +/- 0.171 (for the latter two P less than 0.001), respectively. With AF, transport was inhibited equally in both models during VE. There were no significant differences in the electrolyte composition of AF and HTF during shrinkage as measured by microprobe analysis. The 47% inhibition of Jv with HTF but not AF during VE in the late-clip but not the early-clip rats strongly implies the presence of factors other than physical forces during VE, which inhibit proximal tubular Na transport. Studies of tubular transport during VE need to be performed using both AF and HTF.

Animals↗
PubMed2000

Embolism of a metallic clip: an unusual complication following laparoscopic cholecystectomy.

A 32-year-old woman underwent laparoscopic cholecystectomy during which there was severe bleeding from the bed of the gallbladder. As application of metallic clips to control the bleeding was not successful, the operation was converted to an open laparotomy. Cholecystectomy was successfully completed without further complications, and the post-operative course was uneventful and the patient was discharged. Eighteen months later, the patient complained of dyspnea. Plain radiograph and computed tomography of the thorax showed a metallic clip in the branch of the pulmonary artery supplying the posterior basal segment of the inferior lobe of the left lung. There was no connection between the patient's symptoms and the clip embolism. Nevertheless, clip migration or embolism could cause severe complications. Therefore, metallic clips should not be used to stop bleeding from the gallbladder bed.

Adult↗
PubMedDate not supplied

Prolongation of the saralasin responsive state of two-kidney, one clip Goldblatt hypertension in the rat by the orally administered converting enzyme inhibitor captopril (SQ14,225).

Two-kidney, one clip Goldblatt rats were treated with oral converting enzyme inhibitor captopril (SQ14,225) 6 mg/kg/day for 3 weeks after they had developed hypertension. Before treatment, systolic blood pressure rose from 143 to 202 mm Hg (p less than 0.05). Tail vein infusions of saralasin 10 microgram/kg/min in conscious rats reduced systolic blood pressure from 202 to 121 mm Hg (p less than 0.05) at 8 weeks after clipping the renal artery and before treatment with captopril. Chronic treatment with captopril for 3 additional weeks lowered blood pressure to 173 mm Hg (p less than 0.05). When saralasin infusion was repeated during treatment with captopril, blood pressure fell from 173 to 159 mm Hg (p less than 0.05). Blood pressure rose to 197 mm Hg within 4 days after captopril was discontinued and saralasin infusion 3 weeks after captopril (15 weeks after clipping the renal artery) again resulted in a dramatic fall in blood pressure from 197 to 142 mm Hg (p less than 0.05). Goldblatt rats who had not received captopril showed no blood pressure response to saralasin infusion at 12 weeks after renal artery clipping. The present study demonstrates that partial inhibition of the renin-angiotensin system with captopril results in a delay in the natural evolution of clip hypertension retarding the appearance of hypertension that is resistant to acute saralasin infusion.

Angiotensin II↗
PubMed1988

Renal glomerular atrial natriuretic factor receptors in one-kidney, one clip rats.

One-kidney, one clip (1K1C) hypertension is often associated with an expanded plasma volume and (once the arterial clip is removed) with natriuresis. Blood pressure (BP), atrial and plasma concentrations of atrial natriuretic factor (ANF), hematocrit, and renal glomerular ANF receptors were therefore studied in 1K1C rats and in their normotensive uninephrectomized controls before and after unclipping. Six hours after removal of the clip, BP was normal in the 1K1C group and plasma ANF presented a sharp decline but was still significantly higher than in the normotensive controls, with a slight difference being evident 24 hours after unclipping. Hematocrit was lower in the 1K1C rats than in their control counterparts, but this difference tended to disappear once the clip was removed, indicating a contraction of plasma volume in these unclipped 1K1C animals. The renal glomerular ANF receptor population was markedly smaller in 1K1C rats than in the uninephrectomized controls but showed a twofold increase in number and affinity 24 hours after unclipping. It is concluded that the up-regulation and enhanced affinity of glomerular ANF receptors (probably secondary to the decrease in plasma levels of ANF) may contribute to the natriuresis reported in hypertensive 1K1C animals on removal of the arterial clip.

Animals↗
PubMedDate not supplied

Reversal of two-kidney one clip renovascular hypertension in the rat.

Attempted correction of two-kidney, one clip Goldblatt hypertension in the rat was carried out by three techniques; removal of the constricting clip, removal of the ischemic kidney, and converting enzyme blockade by oral captopril. Since duration of hypertension is said to be a critical factor, groups of rats were studied after short term (less than 6 weeks from clipping) and chronic (greater than 4 months) hypertension. Blood pressure, sodium balance, and plasma renin concentration (PRC) were followed before and after these correcting procedures. In a control group of animals, removal of a loose renal artery clip did not influence blood pressure and only caused trivial postoperative retention of sodium. Unclipping, however, normalized blood pressure in both short-term and chronic hypertension. After a major postoperative fall, blood pressure returned to somewhat elevated levels after nephrectomy in animals with chronic (but not short-term) hypertension. Sodium balance became markedly positive with the fall in blood pressure of operated hypertensive animals and was significantly correlated with the fall in blood pressure of operated hypertensive animals and was significantly correlated with the fall in blood pressure in these four groups at 7 days (r = 0.43). Captopril also produced a fall in blood pressure at 24 hours, with a positive sodium balance, although the relationship between blood pressure fall and sodium balance did not reach statistical significance (r = 0.30). The PRC was elevated in all hypertensive groups, although individual values overlapped with values from normal rats and nonhypertensive rats with a loose renal artery clip. The PRC fell to normal or subnormal values after either operative procedure and stabilized for at least 2 months independently of whether blood pressure fell or not. It is concluded that neither sodium retention nor renin hypersecretion maintains blood pressure in this model. Also, the rapidity of the blood pressure fall is not consistent with a role for vascular hypertrophy. The greater efficacy of unclipping suggests that the revascularized kidney after this procedure exerts a vasodepressor function independent of sodium excretion or the renin-angiotensin system.

Animals↗
PubMed1986

Effects of angiotensin inhibition and renal denervation in two-kidney, one clip hypertensive rats.

Neural and angiotensin-mediated influences that alter hemodynamic and excretory behavior of the nonclipped kidney of two-kidney, one clip hypertensive rats were assessed by sequential acute surgical denervation of the nonclipped kidney and intravenous infusion of converting enzyme inhibitor (SQ 20881), 3 mg/kg X hr. Normal and two-kidney, one clip hypertensive rats (0.2-mm silver clip on the right renal artery 3-4 weeks before study) were prepared to allow study of each kidney. Mean arterial blood pressure of two-kidney, one clip hypertensive rats fell significantly from control values of 149 +/- 6 to 135 +/- 6 mm Hg after denervation of the nonclipped kidney. Despite this decrease in arterial pressure, the nonclipped kidney exhibited significant increases in glomerular filtration rate (from 1.00 +/- 0.08 to 1.24 +/- 0.08 ml/min), sodium excretion (from 88 +/- 39 to 777 +/- 207 nEq/min), fractional sodium excretion (from 0.06 +/- 0.02 to 0.54 +/- 0.14%), and urine flow rate (from 3.7 +/- 0.5 to 8.2 +/- 1.1 microliter/min). A significant decrease in glomerular filtration rate (from 1.12 +/- 0.07 to 0.85 +/- 0.08 ml/min) with no change in excretory function was observed for the clipped kidney following denervation of the nonclipped kidney. Intravenous addition of converting enzyme inhibitor significantly increased renal blood flow (from 7.0 +/- 1.3 to 10.6 +/- 1.5 ml/min) and sodium excretion (from 777 +/- 207 to 1384 +/- 425 nEq/min) for the nonclipped kidney; blood pressure decreased from 135 +/- 6 to 123 +/- 4 mm Hg, and renal vascular resistance decreased significantly (from 22 +/- 3 to 13 +/- 2 mm Hg X min/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed2004

Systolic and diastolic ventricular function assessed by pressure-volume loops in the stage 21 venous clipped chick embryo.

Cardiac pressure-volume relations enable quantification of intrinsic ventricular diastolic and systolic properties independent of loading conditions. The use of pressure-volume loop analysis in early stages of development could contribute to a better understanding of the relationship between hemodynamics and cardiac morphogenesis. The venous clip model is an intervention model for the chick embryo in which permanent obstruction of the right lateral vitelline vein temporarily reduces the mechanical load on the embryonic myocardium and induces a spectrum of outflow tract anomalies. We used pressure-volume loop analysis of the embryonic chick heart at stage 21 (3.5 d of incubation) to investigate whether the development of ventricular function is affected by venous clipping at stage 17, compared with normal control embryos. Steady state hemodynamic parameters demonstrated no significant differences between the venous clipped and control embryos. However, analysis of pressure-volume relations showed a significantly lower end-systolic elastance in the clipped embryos (slope of the end-systolic pressure-volume relation: 5.68 +/- 0.85 versus 11.76 +/- 2.70 mm Hg/microL, p < 0.05), indicating reduced contractility. Diastolic stiffness tended to be increased in the clipped embryos (slope of end-diastolic pressure-volume relation: 2.74 +/- 0.56 versus 1.67 +/- 0.21, p = 0.103), but the difference did not reach statistical significance. The results of the pressure-volume loop analysis show that 1 d after venous obstruction, development of ventricular function is affected, with reduced contractility. Pressure-volume analysis may be applied in the chick embryo and is a sensitive technique to detect subtle alterations in ventricular function.

Animals↗
PubMed1993

Variations in regional cerebral blood flow investigated by single photon emission computed tomography with technetium-99m-d, l-hexamethylpropyleneamineoxime = l-h during temporary clipping in intracranial aneurysm surgery: preliminary results.

Single photon emission computed tomography with technetium-99m-d, l-hexamethylpropyleneamineoxime was used to assess variations in regional cerebral blood flow during temporary clipping in the course of intracranial aneurysm surgery and during the postoperative period in 20 patients, 14 of whom underwent temporary clipping. Of these 14 patients (Group A), 9 had aneurysms of the anterior communicating artery, 2 had aneurysms of the middle cerebral artery, and 3 had aneurysms of the carotid siphon. Temporary clips were applied, according to the site of the lesion, on A1, on the trunk of the middle cerebral artery, or on the trunk of the internal carotid artery. The occlusion time ranged from 2 to 31 minutes. The six patients who did not undergo temporary clipping served as controls (Group B), as follows: three had aneurysms of the posterior communicating artery, one of the anterior communicating artery, one of the middle cerebral artery, and one of the internal carotid artery. All patients were investigated with cerebral single photon emission computed tomography preoperatively, perioperatively, and postoperatively. In all the patients of Group A, the preliminary results of the study show a sharp fall in the perfusion of the territories of the temporarily clipped parent vessel and practically a complete recovery within 2 to 7 days of surgery, with no significant neurological symptoms. No similar disturbance of perfusion was found in the patients of Group B.

Adult↗
PubMed2006

Outcome of surgical clipping of unruptured aneurysms as it compares with a 10-year nonclipping survival period.

OBJECTIVE: Recent studies on the natural history of unruptured intracranial aneurysms dictate that we reevaluate the risks and benefits of surgical intervention as it compares with the natural course. We analyzed the outcome of surgical clipping of a patient cohort with unruptured aneurysms as it compares with a 10 year nonclipping survival period on the basis of two previously published studies (International Study on Unruptured Intracranial Aneurysms and a study by Juvela et al. [36] from Helsinki). METHODS: Data on 148 unruptured aneurysms in 116 consecutive surgically treated patients were prospectively recorded and retrospectively analyzed. The overall majority were diagnosed with cerebral angiography. Data analyzed included aneurysmal properties and clinical outcomes including surgical related mortalities and morbidities. The observed outcomes were compared with the expected outcome of a 10 year nonclipping survival period if the patient cohort was included in recently reported studies on unruptured aneurysms. More than 1 year follow-up was available in 93.1% (108) of patients and follow-up cerebral angiography was performed in 80% (93) of patients. RESULTS: Mean age was 53.57 years. There were 25 (16.8%) small aneurysms (less than 7 mm), 70 (47.2%) aneurysms 7 to 12 mm in size, 41 (27.70%) large (13-24 mm), and 12 (8.10%) giant (>25 mm) aneurysms. Posterior circulation aneurysm comprised 13.51%. One hundred forty-three (96.62%) aneurysms were successfully clipped, and 3.37% were either wrapped or later coiled. Surgical-related mortality was 0.82% (1 patient because of air embolism). Surgical related permanent morbidity was 3.44% (4 patients) and transient surgical-related mild morbidities was 7.7% (9 patients). Immediate postsurgical good outcome (Glasgow Outcome Score = 4-5) was 87.93% (102 patients) and 95.68% in 3 months (111 patients). At 1 year, the modified Rankin scale scores were 0 to I = 102, II = 3, III = 2, IV = 1, and V = 0. Residual aneurysms were seen in none of the postoperative angiograms (93 patients). Using the chi method, the comparison of the expected to the observed mortality and morbidity revealed a statistically significant difference in the mortality in favor of surgical clipping (P = 0.034 when compared with the International Study on Unruptured Intracranial Aneurysms and P = 0.05 when compared with the Juvela et al. [36] study). There was no statistically significant difference in the permanent morbidity. CONCLUSION: Studies on natural history of unruptured intracranial aneurysms suggest 10 year cumulative bleeding-related mortality and severe morbidity of no less than 7.5%. In our study, surgical clipping resulted in an 0.8% rate of mortality and 3.4% permanent morbidity. This suggests that surgical clipping has the potential of a superior outcome to the natural history of patients who have an estimated life expectancy of no less than 10 years.

Adult↗
PubMed2006

Microtubule plus-end loading of p150(Glued) is mediated by EB1 and CLIP-170 but is not required for intracellular membrane traffic in mammalian cells.

Microtubule dynamics and function are regulated, at least in part, by a family of proteins that localize to microtubule plus-ends, and include EB1, CLIP-170 and the dynactin component p150(Glued). Plus-end pools of these proteins, notably dynactin, have been invoked in a number of ;search-and-capture' mechanisms, including the attachment of microtubules to kinetochores during mitosis and to endomembranes prior to the initiation of intracellular transport. Here we show that, in mammalian cells, EB1 is required for the plus-end localization of CLIP-170, and that this is in turn required to localize p150(Glued) to plus-ends. Specific depletion of CLIP-170 results in defects in microtubule dynamics, cell polarization in response to scratch wounding and a loss of p150(Glued) from plus ends. By contrast, removal of p150(Glued) from plus-ends by depletion of either EB1 or CLIP-170 caused no defects in the localization of intracellular organelles, the dynamics of ER-to-Golgi transport, the efficiency of transferrin uptake or the motility of early endosomes or lysosomes. In addition to labelling microtubule plus-ends, we show that GFP-p150(Glued) becomes incorporated into the dynactin complex and labels small, highly dynamic, punctate structures that move along microtubules. A subset of these structures colocalizes with ER-Golgi transport intermediates. Together, these data show that the function of CLIP-170 and p150(Glued) in membrane trafficking is not associated with their plus-end localization.

Biological Transport↗
PubMed2005

Guidelines for filming digital camera video clips for the assessment of gait and movement disorders by teleneurology.

Digital still cameras capable of filming short video clips are readily available, but the quality of these recordings for telemedicine has not been reported. We performed a blinded study using four commonly available digital cameras. A simulated patient with a hemiplegic gait pattern was filmed by the same videographer in an identical, brightly lit indoor setting. Six neurologists viewed the blinded video clips on their PC and comparisons were made between cameras, between video clips recorded with and without a tripod, and between video clips filmed on high- or low-quality settings. Use of a tripod had a smaller effect than expected, while images taken on a high-quality setting were strongly preferred to those taken on a low-quality setting. Although there was some variability in video quality between selected cameras, all were of sufficient quality to identify physical signs such as gait and tremor. Adequate-quality video clips of movement disorders can be produced with low-cost cameras and transmitted by email for teleneurology purposes.

Evaluation Studies as Topic↗
PubMed2001

A national survey of attitudes towards the use of MRI in patients known to have intracranial aneurysm clips.

The objective of this study was to determine the attitudes and practice of neuroradiology centres across the UK regarding the use of MRI in patients known to have intracranial aneurysm clips. A postal survey comprising three questions and a comments section was sent to 35 neuroradiology centres across the UK. There were 32 (91%) respondents to the single questionnaire. 16 (50%) respondents said that they would not consider performing MRI on a patient with an intracranial aneurysm clip. Of the remaining 50%, all said that identification of the clip type and assurance of its safety would be needed prior to scanning the patient. The magnetic strength of the system did not appear to affect the decision regarding whether or not to perform MRI on such patients. There was a variation in attitude towards the use of MRI in such patients between different regions. Neuroradiology centres are equally divided in their attitude and practice about whether it is safe to use MR to image a patient known to have an intracranial aneurysm clip. This is most probably due to the conflicting literature, as well as uncertainty about the identification and ferromagnetic properties of individual clips.

Brain↗
PubMed1998

Regulation of glomerular TGF-beta expression in the contralateral kidney of two-kidney, one-clip hypertensive rats.

Previous studies have demonstrated that angiotensin II stimulates expression of transforming growth factor-beta (TGF-beta) in cultured renal cells. To investigate whether similar mechanisms are operative in vivo, glomerular TGF-beta mRNA expression was investigated in two-kidney, one-clip (2-K 1-C) hypertensive rats. Glomerular TGF-beta1 transcripts were elevated in the clipped kidney 6 d, but not 3 d, after surgery. Later, during the course of the disease (21 to 35 d), TGF-beta1 mRNA was upregulated in contralateral kidneys compared with sham-operated control kidneys. There was no difference in plasma TGF-beta1 levels between 2-K 1-C rats and controls. Treatment with the AT1 receptor antagonist losartan, as well as with triple therapy (hydralazine, reserpine, and hydrochlorothiazide), started 1 d after clipping, significantly reduced systolic BP in hypertensive rats at day 21 after clipping. Both treatments were equally effective in preventing the increase in glomerular TGF-beta1 mRNA and protein expression in the contralateral kidney at day 21. In a second set of experiments, interventional treatment with losartan or triple therapy, starting 14 d after surgery, was investigated. This treatment for 3 wk significantly reduced the increase in TGF-beta1 expression in the contralateral kidney. At day 35 after clipping, considerable glomerular damage and sclerosis were present, mainly in contralateral kidneys. Interventional treatment with losartan or triple therapy partly prevented this glomerular damage of the contralateral kidney. The data demonstrate that TGF-beta1 expression in the contralateral kidney in 2-K 1-C rats is regulated by the increase in systemic BP rather than by direct effects of angiotensin II.

Animals↗