Role of renal prostaglandin E2 in two-kidney, one-clip renovascular hypertension in rabbits

To investigate the role of renal prostaglandin E2 (PGE2) in renovascular hypertension, urinary PGE2 was measured in rabbits with hypertension produced by left renal artery constriction. In the acute phase of renovascular hypertension (1 week after the constriction), urinary excretions of PGE2 and sodium were significantly increased without correlations with changes in the systemic blood pressure (delta BP). In this phase, delta BP was directly proportional to plasma renin activity and plasma aldosterone concentration (p less than 0.001). In the intermediate phase (5 weeks), delta BP lost significant correlations with plasma renin activity and plasma aldosterone concentration and had a inverse correlation with urinary sodium excretion (p less than 0.01). In the maintenance phase (10 weeks), delta BP showed inverse correlations (p less than 0.01) with both PGE2 and sodium excretions, although their excretions decreased to normal levels. In the clipped kidney, only urinary PGE2 excretion in the acute phase was significantly elevated (p less than 0.02), and both sodium and PGE2 excretions were significantly decreased (p less than 0.01) in the maintenance phase. In the nonclipped kidney, urinary PGE2 and sodium excretions were elevated in the acute and intermediate phases, but decreased to the control levels in the maintenance phase. In this phase, delta BP showed inverse correlation (p less than 0.01) with both PGE2 and sodium excretions from the nonclipped kidney. The infusion of saralasin, an angiotensin II analogue, dose dependently reduced the blood pressure in the acute phase, but showed no effect in the intermediate and maintenance phases.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of neuropeptide Y in the development of two-kidney, one-clip renovascular hypertension in the rat

OBJECTIVE: Along with the renin-angiotensin system, sympathetic stimulation may contribute to renovascular hypertension. The vasoactive peptide neuropeptide Y (NPY) is co-released with and potentiates the pressor effects of norepinephrine through the Y-1 receptor. NPY, by exaggerating sympathetic activity, may contribute to renovascular hypertension, possibly by augmenting adrenergic-mediated renin release. This was studied by determining the effect of continuous Y-1 blockade on the development of two-kidney, one-clip renovascular hypertension and the effect of NPY on in vitro renin release. METHODS: Mean arterial pressure and renal blood flow responses to NPY (10 microg/kg, administered intravenously) were measured in five anesthetized Sprague-Dawley rats before and after BIBO3304TF administration to test the Y-1 antagonist BIBO3304TF. In hypertension studies, 28 rats underwent left renal artery clipping. Of these, 13 were implanted with a mini-osmotic pump for continuous BIBO3304TF infusion (0.3 microg/h, administered intravenously); the other 15 underwent sham implantation. Systolic blood pressure was then monitored for 4 weeks. Finally, in vitro renin release was measured from renal cortical slices (n = 6-12) incubated with NPY (10(-8) to 10(-6) mol/L) or NPY plus the adrenergic agonist isoproterenol (10(-4) mol/L). RESULTS: BIBO3304TF attenuated the NPY-induced increase in mean arterial pressure by 54% (P <.02) and the NPY-induced decrease in renal blood flow by 38% (P <.05). In 4-week hypertension studies, systolic blood pressure in clipped controls increased from 130 +/- 3 mm Hg to 167 +/- 6 mm Hg (P <.01), whereas BIBO3304TF-treated rats had no significant increase (125 +/- 3 mm Hg to 141 +/- 8 mm Hg). Final systolic blood pressure was 26 mm Hg lower in BIBO3304TF-treated rats than in controls (P <.01). In renal cortical slices, no NPY effect was observed in basal or isoproterenol-stimulated renin release. CONCLUSIONS: The Y-1 receptor antagonist BIBO3304TF attenuated acute pressor responses to NPY and blunted the development of two-kidney, one-clip renovascular hypertension in rats. NPY may contribute to the hypertensive response in this renovascular hypertension model. Our in vitro data do not suggest that this is due to NPY enhancement of renin release.     

Effects of renal denervation of the contralateral kidney on blood pressure and sodium and eicosanoid excretion in the chronic phase of two-kidney, one-clip renovascular hypertension in rats

OBJECTIVE: To define the role of the renal nerves of the contralateral kidney in the maintenance of two-kidney, one-clip (2K-1C) renovascular hypertension in rats. MATERIAL AND METHODS: The contralateral kidney of 2K-1C rats was denervated 6 months after induction of hypertension and 4 weeks after nephrectomy of the clipped kidney. Blood pressure, sodium and potassium balance and eicosanoid excretion were measured. RESULTS: Denervation of the contralateral kidney induced normalization of blood pressure in post-Goldblatt hypertensive rats. This effect was not mediated by a negative sodium balance. Excretion of prostaglandin E2 and thromboxane B2 increased after denervation of the contralateral kidney in both post-Goldblatt hypertensive and post-Goldblatt normotensive rats, while urine extraction remained unaffected. CONCLUSION: Afferences from the contralateral kidney appear to participate in the maintenance of 2K-1C renovascular hypertension due to the activation of central mechanisms regulating blood pressure.     

Effect of potassium depletion on two-kidney, one-clip renovascular hypertension in the rat

There is considerable controversy about the hemodynamic effect of potassium in hypertension. To determine if K depletion could alter the control of blood pressure, studies were performed in rats with 2-kidney, 1-clip renovascular hypertension (RVH) after 3 to 6 wks of severe and moderate K depletion. After application of a 0.23 mm clip to the left renal artery, rats were placed on a K-replete (KR) (240 mEq/kg), a moderately K-depleted (KDM) (59 mEq/kg), or a severely K-depleted (KDS) (5 mEq/kg) diet. After 3 wks, mean arterial pressure (MAP) reached 154 +/- 3 in KR but only 121 +/- 2 in KDM (P less than 0.01) and 106 +/- 4 mm Hg in KDS (P less than 0.001). After 6 wks, MAP was 160 +/- 8 in KR, but only 132 +/- 5 in KDM (P less than 0.01) and 129 +/- mm Hg in KDS (P less than 0.01). Plasma K at 3 wks was 4.1 +/- .1 in KR, but only 3.5 +/- .1 in KDM (P less than 0.05) and 2.3 +/- .1 mEq/liter in KDS (P less than 0.001). This was associated with an 8% decrease in muscle K in KDM and a 16% decrease in muscle K in KDS. Although KDS animals did not grow during the 6 wks of study, KDM rats gained 60% as much weight at 3 wks, and, by 6 wks, weight gain was comparable in KDM (101 +/- 9) and KR (110 +/- 9 g) animals (P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of sodium and renal prostaglandin E2 in the maintenance of hypertension in the chronic phase of two-kidney one-clip renovascular hypertension in rabbits

To study the role of sodium and renal prostaglandin E2 in the chronic phase of two-kidney one-clip renovascular hypertension, urinary excretion rates of sodium and prostaglandin E2 were measured in rabbits with hypertension induced by left renal artery constriction during alteration in sodium intake. The arterial blood pressure, the increasing rate of body weight and sodium balance during alteration in sodium intake were directly proportional to the amount of sodium intake in the hypertensive rabbits, but not in the control ones. Plasma renin activity and plasma aldosterone concentration, which had no significant difference between hypertensive and control rabbits, were inversely proportional to the amount of sodium intake in both rabbits. Urinary excretion rates of sodium in the clipped kidneys of the hypertensive rabbits were significantly lower than the control values in all dietary regimens (p less than 0.01). Urinary excretion rates of sodium in the nonclipped kidneys were not significantly higher and in the total kidneys were significantly lower than the corresponding control values during sodium load (p less than 0.01). Urinary excretion rates of prostaglandin E2 were inversely proportional to the amount of sodium intake in both groups. Urinary excretion rates of prostaglandin E2 in the clipped kidneys were significantly lower than the control values in all dietary regimens (p less than 0.001). Urinary excretion rates of prostaglandin E2 in the nonclipped kidneys were significantly higher during sodium restriction (p less than 0.01) but not during sodium load than the control values. Furthermore, urinary excretion rates of prostaglandin E2 in the total kidneys were significantly lower than the control values in all dietary regimens (p less than 0.01). These results suggest that two-kidney one-clip renovascular hypertension in rabbits seems to be partly sodium-dependent in the chronic phase because the nonclipped kidney fails to excrete sodium sufficiently. There may also be disorders of renal prostaglandin E2 metabolism influencing these disorders of sodium in the nonclipped kidneys.     

Central catecholamine,sympathetic nerve and vascular protein in the acute phase of two-kidney,one-clip renovascular hypertension in rats

Incorporation of³H-proline into the non-collagenous protein in mesenteric arteries in two-kidney, one-clip hypertensive rats was greater than that in normotensive rats. Splanchnicotomy predominantly over the root of mesenteric arteries or intracranioventricular injection of 6-hydroxydopamine prevented the development of hypertension in 2K-1C rats concomitant with the reduction of incorporation of³H-proline into the non-collagenous protein in mesenteric arteries. The content of norepinephrine in the hypothalamus in 2K-1C rats was lower than that in normotensive control rats. These findings indicate that increased non-collagenous protein synthesis in mesenteric arteries or low level of hypothalamic norepinephrine has facilitative effects on the development of 2K-1C hypertension.     

Effects of eplerenone on heart and kidney in two-kidney, one-clip rats

BACKGROUND: The role of aldosterone has been less investigated compared to the renin-angiotensin-aldosterone system in renovascular hypertension. The purpose of the present study was to compare the effects of a selective aldosterone receptor blocker, eplerenone (EP), and an angiotensin II receptor type 1 antagonist (AT1RA), losartan (LO) on cardiac and renal damage produced by two-kidney, one-clip (2K-1C) renovascular hypertension in rats. METHOD: Wistar rats (n = 48) were placed on one of six groups. Group 1 received sham operation. From group 2 to 6, all rats were made as 2K-1C renovascular hypertension. Group 2 received vehicle. Group 3 orally received 100 mg/kg/day of EP from the initiation of the study. Group 4 received 100 mg/kg/day of LO, from the initiation of the study. Groups 5 and 6 received EP and LO from the 4th week after the clipping respectively. Systolic blood pressure (SBP) and urinary protein excretion (UPE) were measured before and every 2 weeks. The remnant kidney was obtained for histopathological analysis and for measurement of endothelial cell nitric oxide synthase (ecNOS) gene expression (GE). RESULTS: SBP increased in the placebo group (132.1 +/- 2.4 vs. 115.0 +/- 0.6 mm Hg in sham group at week 10, p = 0.019). Treatment with LO or EP from the beginning of the study decreased SBP significantly as measured in the sham group at week 10. The placebo group developed significant UPE (21.7 +/- 1.9 mg/day) compared with the sham group (13.4 +/- 0.8 mg/day, p < 0.05). Treatment with both LO (12.5 +/- 1.5 mg/day, p < 0.01 vs. placebo) and EP (14.8 +/- 1.0 mg/ day, p < 0.05 vs. placebo) significantly decreased UPE. On the other hand, the late start of treatment with EP failed to decrease the increased UPE. UPEs were not significantly different between the LO- and EP-treated groups throughout the study. There was no significant pathological change in heart and kidney in all groups. In heart, ecNOS GE was significantly increased in the EP-treated (from the beginning of the study) rats compared with placebo group (0.47 +/- 0.01 vs. 0.43 +/- 0.01, p < 0.05). LO did not have an effect on ecNOS GE in heart. In aorta, ecNOS GE was significantly increased in the two EP-treated groups compared with the placebo group (0.22 +/- 0.01, 0.22 +/- 0.02 vs. 0.15 +/- 0.01, p < 0.05, respectively). LO also did not have an effect on ecNOS GE in aorta. In kidney, ecNOS GE was significantly increased in the LO group (from the beginning of the study) and two EP-treated groups compared with placebo. CONCLUSION: This study demonstrated that EP treatment significantly reduced SBP and UPE compared with placebo in both development and established 2K-1C renovascular hypertension. EP was as effective as LO in lowering the blood pressure of this renin-dependent animal model.     

Effects of caffeine on the vascular smooth muscles isolated from two-kidney, one-clip renovascular hypertension in rabbits

To examine the intracellular calcium content of the vascular smooth muscle in the chronic phase of renovascular hypertension, the effects of caffeine on isolated aortic, renal and iliac arterial strips were evaluated in two-kidney, one-clip renovascular hypertension in rabbits. 10 weeks after left renal artery constriction in the constricted group, systemic blood pressure (BP) was significantly higher than in the control group, but plasma renin activity was similar to the control value. The amplitude of caffeine-induced contraction of various vascular strips in the constricted group gradually increased and, at 10 weeks, this was higher in the constricted group than in the control group. In the constricted group, sodium loading produced BP elevation and increased the amplitude of caffeine-induced contraction, whereas sodium constriction decreased BP and the amplitude. In the control group, altered sodium intake did not affect BP and the amplitude of caffeine-induced contraction. These results suggest that in the chronic phase of renovascular hypertension, the increased caffeine-sensitive intracellular calcium store on vascular smooth muscle, which is increased by sodium loading and is decreased by sodium restriction, may contribute to the maintenance of hypertension.     

Central noradrenergic neurons and vascular non-collagen protein in the initial phase of two-kidney,one-clip renovascular hypertension

Rats had been given intraventricular injection of 6-hydroxydopamine (6-OHDA) before clipping the unilateral renal artery (2K-1C) that caused selective ablation of the central noradrenergic neurons. Central catecholamines and thein vivo incorporation of³H-proline into vascular non-collagen protein were determined in 2K-1C rats in the acute hypertensive stage. It is suggested that increased non-collagen protein synthesis in the mesenteric artery and the low level of hypothalamic norepinephrine concentration may participate in the development of 2K-1C hypertension in rats.     

The effect of exogenous nitric oxide on endothelial dysfunction in two-kidney, one-clip renovascular hypertensive rats

Previous studies have shown that hypertension causes endothelial dysfunction. To study the influence of exogenous nitric oxide(NO) on endothelial dysfunction produced by hypertension, we administered a non-depressor dose of nipradilol to two-kidney, one-clip renovascular hypertensive rats(2K1C). Sprague-Dawley rats underwent either sham surgery(G-1) or clipping of the left renal artery. From day seven, 2K1C were randomized into 3 groups, placebo treatment(G-2), nipradilol treatment(G-3,) and propranolol treatment(G-4). Urinary NO2- + NO3-(NOx) excretion (UNOx V) was measured 4 weeks after clipping, and then, acetylcholine(Ach), A23187, or sodium nitroprusside(SNP)-induced relaxation were measured in the aorta. Blood pressure was increased in G-2, G-3, and G-4 compared to G-1. UNOx V was lower in G-2, G-3, and G-4 compared to G-1, but UNOx V was higher in G-3 compared to G-2 and G-4. Although Ach or A23187-induced relaxation was significantly decreased in isolated artery from G-2, G-3, and G-4 compared with those from G-1. Ach- or A23187-induced relaxation was improved in G-3. SNP-induced relaxation did not differ among the 4 groups. These results suggest that exogenous NO from nipradilol reduces the endothelial dysfunction caused by hypertension without changing the blood pressure.     

Renal expression of aminopeptidase A in rats with two-kidney, one-clip hypertension.

BACKGROUND: Angiotensin II (ANG II) is a major factor involved in the progression of chronic renal disease. Although the generation of this vasoactive peptide has been investigated in great detail, only a few studies have hitherto addressed the metabolism of ANG II into fragments such as angiotensin III and IV (ANG III, IV) which may exert physiological effects independent of ANG II. Aminopeptidase A (APA) is the major enzyme degrading ANG II. The aim of the current study was to evaluate glomerular APA expression in rats with two-kidney, one-clip hypertension. METHODS: The left renal artery was restricted with a 0.2-mm silver clip. Kidneys were harvested 1 and 4 weeks after surgery. APA enzyme and protein expression was evaluated in kidney sections. Total APA enzyme activity and mRNA expression was assessed in isolated glomeruli. Degradation of exogenous ANG II by isolated glomeruli was measured with reverse-phase high-performance liquid chromatography. RESULTS: APA enzyme activity, protein, and mRNA expression were stimulated in the clipped kidney 1 week after surgery compared with the contralateral kidney or normal controls. In contrast, 4 weeks after clipping APA activity and expression was higher in the contralateral kidney. In parallel to these findings, degradation of ANG II was greatest in isolated glomeruli obtained from the clipped kidney after 1 week. However, preparations from the contralateral kidney 4 weeks after surgery were more active in the metabolism of exogenous ANG II. CONCLUSION: The present study provides evidence that APA is complexly regulated in in vivo situations with an activated local renin-ANG II system. ANG II appears to play a direct role in this regulation. However, since conversion of ANG II to ANG III by APA is the initial step leading to the formation of ANG IV which may exert detrimental effects not mediated through classical ANG II receptors, a local increase in APA activity may contribute to the progression of chronic renal disease even during complete AT(1)-receptor blockade.     

Effects of nifedipine on renal cortical and medullary blood flow in two-kidney, one-clip renovascular hypertension in rabbits

The effects of nifedipine, a calcium antagonist, on blood pressure and renal regional blood flow were investigated in two-kidney, one-clip renovascular hypertensive rabbits. At 1 week after left renal artery constriction, in the constricted group, systemic blood pressure (BP) significantly rose with the elevation of plasma renin activity (PRA). In both kidneys, renal vascular resistance (RVR on the constricted group was significantly increased as compared to that in the control group. In the clipped kidney, total renal blood flow (RBF) and renal cortical blood flow (RCBF) of the constricted group were significantly decreased, while renal medullary blood flow (RMBF) remained at the control value. In the nonclipped kidney, RBF and RCBF of the constricted group did not significantly change, and RMBF was significantly increased as compared to that of the control group. After administration of nifedipine for 1 week (1.0 mg/kg/day), BP in the constricted group was decreased to the control level and PRA in both groups was increased. The percent change of BP in the constricted group was significantly decreased and the percent change of PRA in the constricted group was significantly increased as compared to those in the control group. Nifedipine increased RBF, RCBF and RMBF and decreased RVR of both kidneys in each group. In the nonclipped kidney, the percent change of RBF, RCBF and RMBF of the constricted group was significantly increased and the percent change of RVR was significantly decreased as compared to those of the control group. In the clipped kidney, only the percent change of RBF of the constricted group was significantly lower than that in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Different levels of hypertension induce opposite diuretic behaviors from the nonclipped kidney in the rat two-kidney, one-clip model

This study was carried out on conscious two-kidney, one-clip (2K1C) rats to establish whether different levels of hypertension induced opposite diuretic behaviors from the nonclipped kidney. Mildly hypertensive rats and severely hypertensive rats were produced by, respectively, constricting their right renal arteries with 0.3-mm and 0.15-mm clips. On the 11th day of the study, the systolic blood pressure (SBP) of the 0.3-mm clip rats was 150 +/- 2 mm Hg, the water intake was 24 +/- 1 ml, and the urine output was 7 +/- 1 ml. The SBP of the 0.15-mm clip rats was 231 +/- 10 mm Hg, the water intake was 46 +/- 4 ml, and the urine output was 27 +/- 6 ml. The data from the two groups are significantly different. On the 19th day half of the mildly hypertensive (0.3-mm clip) rats that received cilazapril from day 15 had, with respect to their water-treated counterparts, a SBP of 140 +/- 8 as compared with 159 +/- 7 mm Hg, the water intake was 37 +/- 5 as compared with 26 +/- 4 ml, and the urine output was 18 +/- 4 as compared with 12 +/- 1 ml. In contrast, half of the severely hypertensive (0.15-mm clip) rats that received cilazapril had, with respect to their water-treated counterparts, a SBP of 143 +/- 4 as compared with 227 +/- 10 mm Hg, the water intake was 30 +/- 2 as compared with 51 +/- 9 ml, and the urine output was 8 +/- 2 as compared with 29 +/- 4 ml. All changes induced by cilazapril are significant in both groups. The data of this study suggest that different levels of hypertension in the rat 2K1C model induce opposite water elimination modes from the nonclipped kidney. This conclusion is supported by the different shift in the water intake and urine output among the cilazapril-treated rats of the two groups. This contrast in the response to cilazapril seems to be dependent on the magnitude of the resulting hypotension. Thus, it seems that in this model, when the hypertension is mild, the antidiuretic effect of angiotension II on the nonclipped kidney is exhibited, whereas, when the hypertension is severe, the diuretic influence of the blood pressure is evident. Irrespective of these different characteristics of the submodels of 2K1C, angiotensin I converting enzyme inhibitors, such as cilazapril, are effective in normalizing the blood pressure.     

Effects of antihypertensive treatment in one-clip, two kidney hypertension in rats

In order to investigate the consequences of antihypertensive therapy on hormonal and renal parameters in one-clip, two kidney renovascular hypertension, we compared the effects of converting enzyme inhibition (CEI) with those of tripletherapy (clonidine, dihydralazine and furosemide) in this experimental model in rats. The treatment period was initiated four weeks after application of the clip and was continued for five weeks. In plasma, renin was increased and renin substrate was negatively correlated to plasma renin. Hypertension was associated with activation of the renin angiotensin system in both plasma and kidney. The degree of activation of the renin-angiotensin system in the clipped kidney and its suppression in the unclipped kidney was evaluated by two methods, renal renin content and semi-quantification of juxtaglomerular hyperplasia by immunofluorescent renin. These two methods were correlated. During the treatment period, average systolic blood pressure was 144 +/- 13 mmHg in the CEI treated group (HT1) which was not significantly different from the value found in the sham-operated group (139 +/- 4 mmHg; C2). Blood pressure, however, was lowered only to 173 +/- 18 mmHg in the group treated with tripletherapy (HT2). In control hypertensive animals, the wt of the clipped kidney did not decrease whereas significant hypertrophy was present in the unclipped kidney. Tripletherapy did not alter this relationship, whereas converting enzyme inhibition decreased kidney wt in the clipped kidney and increased further the hypertrophy of the contralateral unclipped kidney. A histological examination revealed that hypertensive microangiopathy was a predominant feature in the unclipped kidney of the untreated hypertensive group and of the group treated with tripletherapy, these lesions were completely absent in the CEI treated group. In the CEI treated group, however, ischemic lesions during this treatment were found to be decreased in the contralateral unclipped kidney and increased in the clipped kidney by comparison with untreated hypertensive rats. These renal lesions observed in the clipped kidney were most likely related to the normalization of blood pressure or to a disturbance of intrarenal mechanisms normally mediated by the renin-angiotensin system during stenosis of a renal artery.     

Leukocyte infiltration and ICAM-1 expression in two-kidney one-clip hypertension

How an increase in blood pressure, in and of itself, induces hypertensive nephrosclerosis is unclear. In an earlier study we found that leukocyte infiltration, proximal tubular cell proliferation, matrix deposition and interstitial fibrosis occur in the unclipped kidney of 2 K 1 C Goldblatt hypertensive rats. In this study we tested the hypothesis that the cell surface adhesion molecule ICAM-1 is expressed on the vascular endothelium and tubular epithelium of unclipped kidneys at 4 weeks. As a positive control, we examined the clipped kidney as well. We found that systolic blood pressure was significantly elevated in renovascular hypertensive rats compared to sham-operated controls after 4 weeks (198 ± 5 mmHg vs 121 ± 2 mmHg, P <0.001). Furthermore, quantitative (densitometry) measurements showed that ICAM-1 expression on vascular endothelium and on tubular cells was significantly increased in unclipped kidneys compared to controls (P <0.05). The same was true for monocyte and granulocyte infiltration (P <0.05). These same variables were even more prominent in the clipped kidneys, compared to unclipped and control kidneys (P < 0.05). Our data show that ICAM-1 is expressed in unclipped kidneys exposed to hypertension as well as in clipped kidneys exposed to ischemia. We suggest that mechanical injury induced by increased blood pressure is responsible for an inflammatory adhesion molecule-mediated response and concomitant renal injury.     

The change of vascular reactivity to angiotensin II and norepinephrine in the two-kidney, one-clip renovascular hypertensive rabbit

The change of the response to angiotensin II (AII) and norepinephrine (NE) was evaluated in vivo and vitro in the chronic phase of two-kidney, one-clip renovascular hypertensive rabbits. In the constricted group, systemic blood pressure (BP) was significantly higher and plasma renin activity (PRA) was significantly lower than in the control group. Subpressor doses of AII and NE injections in the constricted group produced significant elevations of BP. In the aortic, renal and iliac arterial strips, the reactivity to AII (10(-10) to 10(-8) M) and NE (10(-10) to 10(-7) M) was significantly increased in the constricted group as compared to the control group. In the constricted group, sodium loading produced BP elevation with decreased PRA and shifted the dose-response curves by AII and NE to the left, whereas sodium restriction decreased BP and shifted the curves to the right. In the control group, altered sodium intake did not affect BP but affected only the dose-response curves by AII. These results suggested that in the chronic phase of renovascular hypertensive rabbits, the increased reactivity to AII and NE may contribute to the maintenance of hypertension.     

Renal tissue and urinary kallikrein activity in two-kidney, one-clip hypertensive rats

Renal tissue and urinary kallikrein activity were studied to assess the role of the renal kallikrein-kinin system in two-kidney, one-clip hypertensive rats. Body weight, urine volume, systolic blood pressure and urinary kallikrein activity were measured in 11 hypertensive rats and 6 normotensive rats 1, 4, 8 and 12 weeks after clipping or sham operation. The hypertensive rats used in the present study had systolic blood pressures of over 180 mm Hg 12 weeks after the operation and presented polyuria with a reduction in weight gain, which placed them in the malignant hypertension category. Urinary kallikrein activity in hypertensive rats significantly decreased from 21.7 +/- 13.3 nkat/day at 1 week to 11.6 +/- 5.5 nkat/day at 12 weeks after clipping (p less than 0.05), while urinary kallikrein activity in normotensive rats significantly increased from 23.6 +/- 8.9 nkat/day at 1 week to 43.7 +/- 16.2 nkat/day at 4 weeks after the sham operation. Significant differences were observed in urinary kallikrein activity between hypertensive rats and normotensive rats 4 and 12 weeks after the operation (p less than 0.05). Renal tissue kallikrein activity from bilaterally nephrectomized kidneys was investigated 12 weeks after the operation. No significant difference in tissue kallikrein activity was found between the two kidneys of the hypertensive rats. However, tissue kallikrein activity was significantly lower in the contralateral kidney of hypertensive rats as compared to the same kidney of normotensive rats (2.13 +/- 0.73 nkat/g in hypertensive rats vs. 3.05 +/- 0.69 nkat/g in normotensive rats, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)