Chemical Renal Medullectomy; Effect upon Reversal of Two-Kidney, One-Clip Hypertension in the Rat

1981 ◽  
Vol 61 (s7) ◽  
pp. 335s-338s ◽  
Author(s):  
R. F. Bing ◽  
G. I. Russell ◽  
J. D. Swales ◽  
H. Thurston ◽  
A. Fletcher

1. Chemical renal medullectomy was produced in rats by injection of 2-bromoethylamine hydrobromide. Plasma creatinine and blood pressure were unchanged although urine volume was increased fourfold. 2. Left renal artery constriction resulted in similar degrees of hypertension in both intact and medullectomized rats. This was associated with a significantly smaller rise in plasma renin concentration in the latter. 3. Blood pressure in conscious intact hypertensive rats became normal within 24 h of unclipping whereas blood pressure of medullectomized rats remained significantly elevated. 4. The presence of an intact renal medulla is essential to the complete reversal of two-kidney, one-clip hypertension in the rat. This may reflect the loss of a medullary vasodepressor system.

1972 ◽  
Vol 42 (6) ◽  
pp. 651-664 ◽  
Author(s):  
G. Bianchi ◽  
E. Baldoli ◽  
R. Lucca ◽  
P. Barbin

1. The renal artery was constricted leaving the opposite kidney intact in ten conscious and seven anaesthetized dogs. Intravenous infusion of exogenous renin was done in seven conscious dogs; in four of these the renal artery was constricted 15–17 days later. The following variables were measured in all animals before and after renal artery constriction: plasma renin concentration, blood pressure, cumulative sodium balance, plasma volume, extracellular fluid volume and plasma non-protein nitrogen. Before and after renal artery constriction in the conscious dogs cardiac output, stroke volume, total peripheral resistance and cardiac rate were also measured. In a few dogs angiotensin responsiveness and plasma concentration of renin substrate were also measured. 2. There was no significant difference between the regression of change in blood pressure on change in plasma renin concentration within 2 h from renal artery constriction in the conscious dogs and that observed during intravenous infusion of renin. Comparing the changes of these variables with the ones previously obtained with renal artery constriction to the lone remaining kidney, for a given increase of plasma renin concentration the rise of blood pressure was lower when the contralateral kidney was untouched. The changes of the other variables in the conscious dogs may be divided into three phases: a first phase lasting hours, in which, besides the changes described above, there was an increase of total peripheral resistance while the other variables remain unchanged: a second phase, 24 h after constriction, in which blood pressure, total peripheral resistance and plasma renin clearance decreased while plasma volume, cardiac output and extracellular fluid volume slightly increased; however, only the plasma volume change was statistically significant: and a third phase 6–7 days after constriction, when all the variables returned towards normal values, except that the blood pressure and total peripheral resistance remained significantly higher. Sodium balance remained at equilibrium throughout the study period. It is suggested that these results are compatible with the ‘autoregulation theory’ of renal hypertension. 3. Renal artery constriction in the anaesthetized animals caused a slight but significant sodium retention that very likely influenced the sequence of the events. On the second day after constriction, the plasma renin concentration was significantly increased, whereas the highest values of blood pressure, plasma volume and extracellular fluid volume occurred on the seventh day after constriction.


1984 ◽  
Vol 67 (5) ◽  
pp. 521-528 ◽  
Author(s):  
D. Taverner ◽  
R. F. Bing ◽  
A. Fletcher ◽  
G. Russell ◽  
J. D. Swales ◽  
...  

1. The rat renal papilla was selectively destroyed by 2-bromoethylamine hydrobromide; increasing doses produced a graded severity of histological damage, polyuria and a reduction in urinary prostaglandin E2 excretion. 2. Destruction of at least half of the papilla caused significant hypertension, but plasma renin concentration and plasma creatinine did not change. 3. After graded medullary damage Goldblatt two-kidney, one-clip hypertension was induced. Four weeks later the severity of hypertension was similar in medulla-damaged and medulla-intact groups. 4. When Goldblatt two-kidney, one-clip hypertension was reversed by removal of the renal artery clip, the blood pressure fall was less when the inner renal papilla was ablated than when it was intact, although plasma renin concentration and sodium balance were similar. The final blood pressure was similar to that observed in normal rats treated with 2-bromoethylamine compared with their respective controls. 5. These findings are consistent with the hypothesis that the inner renal medulla produces a vasodepressor that influences blood pressure in normal rats, and also lowers blood pressure when two-kidney, one-clip hypertension is reversed surgically.


1984 ◽  
Vol 66 (4) ◽  
pp. 473-480 ◽  
Author(s):  
Robert F. Bing ◽  
John D. Swales ◽  
David Taverner ◽  
Herbert Thurston

1. Pressor responses to angiotensin II and noradrenaline have been examined in two models of renovascular hypertension (two-kidney one-clip and one-kidney one-clip) before and 24 h after removal of the renal artery clip to examine the possible role of pressor hyper-responsiveness in the maintenance of hypertension. Early and chronic hypertension was studied to assess the part played by progressive structural hypertrophy. 2. Plasma renin concentration was elevated in early two-kidney hypertensive rats, whereas it was similar to that in age-matched normal rats in early one-kidney and chronic two-kidney hypertensive rats. Twenty-four hours after unclipping plasma renin concentration was the same in all groups. Unclipping restored blood pressure to normal levels by 24 h, whereas sham-operated animals remained hypertensive. 3. Angiotensin II responses in both early and chronic two-kidney one-clip hypertensive rats were lower than in age-matched normal rats. In unclipped rats responses were similar to those in normals. One-kidney hypertensive rats had similar angiotensin II responses to normal rats and there was no change with unclipping. Blockade of endogenous angiotensin II production by converting enzyme inhibition resulted in similar angiotensin II responses in hypertensive and unclipped groups. 4. In normal rats, angiotensin II responses were inversely related to plasma renin concentration (r = −0.47, P<0.001). Angiotensin II responses in hypertensive and unclipped rats were found to show a similar relationship to plasma renin concentration as normal rats. 5. Noradrenaline responses in hypertensive rats were similar to those in age-matched normals and there was no significant change with unclipping. In normal rats there was no relationship between noradrenaline responses and plasma renin concentration (r = −0.11, P<0.5). 6. These results emphasize the importance of the activity of endogenous renin-angiotensin in determining angiotensin II responses in vivo. It is concluded that neither the maintenance of hypertension nor the fall in blood pressure produced by removal of the renal artery clip in renovascular hypertension is due to changes in responsiveness to angiotensin II.


Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Nirupama Ramkumar ◽  
Deborah Stuart ◽  
Matias Calquin ◽  
Shuping Wang ◽  
Fumio Niimura ◽  
...  

It is unknown if intrarenal generation of angiotensinogen (AGT) is important in blood pressure (BP) regulation. Previous studies showed that proximal tubule-specific overexpression of AGT increases BP, while proximal tubule-specific deletion of AGT using the KAP promoter-Cre transgene did not alter BP. The latter study may not have completely eliminated nephron AGT production; in addition, BP was only assessed on a normal salt diet. To evaluate this issue in greater detail, we developed mice with inducible nephron-wide AGT deletion. Mice were generated which were hemizygous for the Pax8-rtTA and LC-1 transgenes and homozygous for loxP flanked AGT alleles to achieve nephron-specific AGT disruption after doxycycline induction. Adult Pax8-rtTA/LC-1/floxed AGT mice at 3 months of age were treated with doxycycline 2 mg/ml in drinking water for 11 days and studied 4 weeks after treatment. Blood pressure (recorded via telemetry) and metabolic balance studies were determined during 5 days of normal, high and low Na diets. Compared to controls, AGT knockout (KO) mice demonstrated significantly lower systolic, diastolic, and mean BPs on all three diets (N=4 each group). The BP reduction was most evident on a low Na diet (mean BP 107 ± 2 mmHg in controls and 88 ± 13 mmHg in AGT KO). Plasma renin concentration was higher in the AGT KO mice as compared to controls on all three diets. There were no detectable differences in weight, urine volume, urine osmolality or urine Na excretion between the controls and KO mice on all three diets, however due to variability, small differences in these parameters may not have been detected. Taken together, these data suggest that nephron AGT may contribute to BP regulation and this is most evident during low Na intake.


1970 ◽  
Vol 38 (6) ◽  
pp. 741-766 ◽  
Author(s):  
G. Bianchi ◽  
L. Tilde Tenconi ◽  
R. Lucca

1. The renal artery to a lone remaining kidney was constricted in fourteen concious dogs. The following variables were measured in all animals: blood pressure (BP), cardiac rate (CR), plasma renin concentration (PRC), plasma volume (PV), extracellular fluid volume (ECFV) and plasma non-protein nitrogen (NPN). Sodium balance was estimated in eleven dogs. Cardiac output (CO), total peripheral resistence (TPR) and stroke volume (SV) were measured in nine dogs. Angiotensin responsiveness (AR) was measured in six animals. 2. Within 2 hr the following changes occurred: a sharp increment of BP, PRC and TPR, with initial reduction or no change in CO and CR; SV and PV were not changed. The linear regression of BP changes on PRC changes did not differ statistically from the one previously obtained during the infusion of exogenous renin in the conscious dog. AR was much depressed at 2 hr. 3. After 24 hr a slight but significant sodium retention developed, while PV and ECFV and SV increased, CO remained unchanged owing to a decrease of CR. PRC tended to return toward normal while BP remained high. Thus the linear regression between these two variables disappeared. At this stage AR increased toward normal and in two dogs exceeded normal. 4. On days 3–4 and 6–7 after constriction, CO increased owing to a rise of SV, while TPR decreased. PV and ECFV were expanded while sodium balance was maintained. AR varied very much in the individual dogs according mainly to changes of PRC, sodium balance and PV. 5. On days 12–14 sodium balance became positive again, PRC returned within normal levels in almost all the dogs. PV and ECFV also tended to decrease to normal. CO and AR were measured in only two dogs at this stage. 6. It is suggested that the early rise of blood pressure might be produced by the increase of PRC, while 3–6 days after the constriction the expansion of PV with the increase of CO contributed to the maintenance of the hypertension.


1977 ◽  
Vol 52 (1) ◽  
pp. 107-109
Author(s):  
M. Fernandes ◽  
G. Onesti ◽  
R. Fiorentini ◽  
A. B. Gould ◽  
K. E. Kim ◽  
...  

1. Propranolol was administered to groups of mature rats before and during the development of renal hypertension induced by ligation of the aorta between the renal arteries. 2. At a dose 10 μmol (3 mg) of propranolol/kg, administered by intraperitoneal injection, the onset and severity of hypertension were not affected, although plasma renin concentration was significantly lower than in the untreated hypertensive rats in the first 5 days after the operation. 3. With 200 μmol (60 mg) of propranolol/kg, administered in the drinking water, peak blood pressure 5 days after aortic ligation was lower than in the untreated control rats, but plasma renin concentration was no lower than with the smaller dose. 4. The development of severe hypertension despite reduction in plasma renin concentration on the low dose of propranolol suggests the participation of renal vasopressor factors other than renin in this model. 5. A higher dose of propranolol reduced the rise in plasma concentration to an equal extent but the rise of blood pressure at 5 days was also reduced, which supports this concept.


1977 ◽  
Vol 18 (3) ◽  
pp. 392-397 ◽  
Author(s):  
Chun Ho PAK ◽  
Masato MATSUNAGA ◽  
Jin YAMAMOTO ◽  
Jun KIRA ◽  
Koichi OGINO ◽  
...  

1983 ◽  
Vol 65 (1) ◽  
pp. 33-36 ◽  
Author(s):  
Joan M. Brice ◽  
G. I. Russell ◽  
R. F. Bing ◽  
J. D. Swales ◽  
H. Thurston

1. Blood pressure, plasma and aortic renin concentrations were measured in Goldblatt two-kidney one-clip hypertensive rats before and after surgical correction by removing the renal artery clip. 2. Blood pressure fell rapidly in the first hour and then more slowly over 24 h. 3. Plasma renin concentration fell into the normal range by 3 h after unclipping. 4. Aortic renin concentration was markedly raised in hypertensive rats and declined slowly after unclipping, being virtually unchanged at 3 h and reaching normal levels at 24 h. 5. The fall in blood pressure produced by removal of the renal artery clip in Goldblatt two-kidney one-clip hypertensive rats does not depend upon the renin-angiotensin system in plasma and vascular tissue and indicates that a renal vasodepressor system may be involved.


1981 ◽  
Vol 97 (4) ◽  
pp. 525-532 ◽  
Author(s):  
Hiromichi Suzuki ◽  
Kazuoki Kondo ◽  
Takao Saruta

Abstract. The present study was performed to assess the influence of potassium on blood pressure in deoxycorticosterone (DOCA) salt hypertensive rats. The effects of potassium administration on the systolic blood pressure, fluid intake, urine volume, excretion of sodium and potassium, serum sodium and potassium, plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were investigated both during the first 2 weeks of development of DOCA salt hypertension and during the next 2 weeks of established DOCA salt hypertension. Potassium administration prevented the development of DOCA salt hypertension and reduced the blood pressure in established DOCA salt hypertension. Fluid intake, urine volume, and excretion of sodium and potassium appeared to be markedly increased in rats treated with potassium. The levels of serum sodium and potassium were unchanged by potassium loading. Both the PRA and PAC which were suppressed in DOCA salt hypertensive rats, were reversed in rats treated by potassium loading. It is suggested that the elevation of blood pressure may be prevented and the increased blood pressure reduced mainly by the diuresis and natriuresis caused by potassium loading.


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