Effect of Unclipping on Pressor Responses in Rats with Renovascular Hypertension

1984 ◽  
Vol 66 (4) ◽  
pp. 473-480 ◽  
Author(s):  
Robert F. Bing ◽  
John D. Swales ◽  
David Taverner ◽  
Herbert Thurston
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Renal Artery ◽  
Renovascular Hypertension ◽  
Plasma Renin ◽  
Chronic Hypertension ◽  
Hypertensive Rats ◽  
Plasma Renin Concentration ◽  
Pressor Responses

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.

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
Keyword(s):  
Blood Pressure ◽  
Renal Artery ◽  
Urine Volume ◽  
Renal Medulla ◽  
Plasma Renin ◽  
Left Renal Artery ◽  
Hypertensive Rats ◽  
Plasma Renin Concentration ◽  
Complete Reversal ◽  
Renal Artery Constriction

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.

Hemodynamic changes induced by reversal of early and late renovascular hypertension

1983 ◽  
Vol 245 (5) ◽  
pp. H734-H740
Author(s):  
G. I. Russell ◽  
R. F. Bing ◽  
J. D. Swales ◽  
H. Thurston
Keyword(s):  
Blood Pressure ◽  
Renovascular Hypertension ◽  
Early Phase ◽  
Peripheral Resistance ◽  
Chronic Phase ◽  
Plasma Renin ◽  
Chronic Hypertension ◽  
Radioactive Microspheres ◽  
Hemodynamic Changes ◽  
Rapid Reduction

The hemodynamic changes associated with reversal of Goldblatt two-kidney, one-clip hypertension in conscious rats were studied using radioactive microspheres. In both the early phase (less than 6 wk from clipping) when plasma renin was elevated and the chronic phase (greater than 4 mo) when plasma renin was normal, hypertension was maintained by elevated peripheral resistance. Unclipping or removal of the ischemic kidney normalized blood pressure within 24 h by reduction in peripheral resistance. In early-phase hypertension blood pressure remained normal at 60 days after nephrectomy or unclipping, but in chronic-phase hypertension blood pressure was significantly elevated at 60 days after nephrectomy despite a similar fall in peripheral resistance. Plasma renin fell to normal or subnormal values after reversal in both early and chronic hypertension. Thus reversal of hypertension is associated with a rapid reduction in peripheral resistance even in longstanding hypertension. Since removal of the ischemic kidney and unclipping were equally effective, reversal must depend on either inhibition of a pressor system derived from the ischemic kidney or activation of a peripheral vasodepressor system not dependent on a revascularized kidney.

Inactivation of Bradykinin and Angiotensin I Conversion in Conscious Rats with Two-Kidney, One-Clip Hypertension

1982 ◽  
Vol 63 (s8) ◽  
pp. 199s-201s ◽  
Author(s):  
Inge E. K. Trindade ◽  
Eduardo M. Krieger
Keyword(s):  
Enzyme Activity ◽  
Angiotensin Ii ◽  
Mean Arterial Pressure ◽  
Renal Artery ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Hypertensive Rats ◽  
Angiotensin I ◽  
Parallel Increase

1. The extents of pulmonary degradation of bradykinin (BK) and angiotensin I (ANG I) to angiotensin II (ANG II) conversion were measured simultaneously to determine whether converting enzyme activity, in vivo, is altered in two-kidney, one-clip hypertensive rats (15, 60 and 180 days after renal artery clipping). 2. Inactivation of BK (estimated by comparing equipressor doses injected intravenously and intra-aortically) was markedly increased in these hypertensive rats: 98.5% (15 days), 98.4% (60 days) and 99.5% (180 days) vs 95.6% in control rats. All groups of hypertensive rats exhibited hyper-reactivity to intra-aortic BK, requiring doses 14–38 times smaller than the control rats to produce the same depressor response. 3. The percentage of ANG I conversion (calculated from equipressor doses of ANG I and ANG II injected intravenously) was elevated after 15 days (46.0% vs 28.1% in control rats), unchanged after 60 days (27.7%) and slightly elevated after 180 days (36.0%). Hyporeactivity to ANG II was observed 15 and 180 days after renal artery clipping (doses six times were needed to produce a standard increase in mean arterial pressure). No alterations were found in the rats at 60 days after artery clipping. 4. The increased degradation of BK cannot be explained solely by elevation of converting enzyme activity since no parallel increase in ANG I conversion was observed, indicating that other bradykininases in the lung may be involved.

scholarly journals Autophagy inhibition by chloroquine prevents increase in blood pressure and preserves endothelial functions

2020 ◽  
Vol 19 (4) ◽  
pp. 789-796
Author(s):  
Moon Jain ◽  
Hina Iqbal ◽  
Pankaj Yadav ◽  
Himalaya Singh ◽  
Debabrata Chanda ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cell Migration ◽  
Endothelial Cell ◽  
Angiotensin Ii ◽  
Ang Ii ◽  
Hypertensive Rats ◽  
Autophagy Flux ◽  
Endothelial Functions

Purpose: To determine the effects of lysosomal inhibition of autophagy by chloroquine (CHQ) onhypertension-associated changes in the endothelial functions. Method: Angiotensin II (Ang II)-treated human endothelial cell line EA.hy926 and renovascularhypertensive rats were subjected to CHQ treatment (in vitro: 0.5, 1, and 2.5 μM; in vivo: 50 mg/kg/dayfor three weeks). Changes in the protein expressions of LC3b II (autophagosome formation marker) andp62 (autophagy flux marker) were assessed using immunoblotting. Cell migration assay, tubuleformation assay (in vitro), and organ bath studies (in vivo) were performed to evaluate the endothelialfunctions. Hemodynamic parameters were measured as well. Results: A higher expression of LC3b II and a reduced expression of p62 observed in the Ang II-treatedendothelial cells, as well as in the aorta of the hypertensive rats, indicated enhanced autophagy.Treatment with CHQ resulted in reduced autophagy flux (in vitro as well as in vivo) and suppressed AngII-induced endothelial cell migration and angiogenesis (in vitro). The treatment with CHQ was alsoobserved to prevent increase in blood pressure in hypertensive rats and preserved acetylcholineinducedrelaxation in phenylephrine-contracted aorta from the hypertensive rats. In addition, chloroquineattenuated Ang II-induced contractions in the aorta of normotensive as well as hypertensive rats. Conclusion: These observations indicated that CHQ lowers the blood pressure and preserves thevascular endothelial function during hypertension. Keywords: Angiotensin II, Autophagy, Chloroquine, Endothelial function, Hypertension, Vasculardysfunction

Renal actions of angiotensin II in renovascular hypertension

1987 ◽  
Vol 65 (8) ◽  
pp. 1559-1565 ◽  
Author(s):  
W. P. Anderson ◽  
R. L. Woods ◽  
K. M. Denton ◽  
D. Alcorn
Keyword(s):  
Angiotensin Ii ◽  
Renal Artery ◽  
Glomerular Filtration ◽  
Renal Artery Stenosis ◽  
Renovascular Hypertension ◽  
Plasma Renin ◽  
Artery Stenosis ◽  
Filtration Fraction ◽  
Severe Stenosis ◽  
Glomerular Ultrafiltration

In renal artery stenosis severe enough to cause hypertension, angiotensin II maintains glomerular filtration rate (GFR) both in the initial high renin phase of hypertension and later when plasma levels are normal. Angiotensin II also maintains GFR in less severe stenosis, which does not cause hypertension. This homeostatic action of angiotensin II to maintain GFR has minimal effects on blood flow. In renal-wrap hypertension, plasma renin levels are elevated for longer than after renal artery stenosis, but in other respects this initial phase of the hypertension is similar to that after renal artery stenosis. GFR is reduced, the rate of development of hypertension is accelerated by angiotensin II, and angiotensin II maintains the glomerular filtration fraction. Renal resistance is markedly increased owing to both compression of the kidney by the hypertrophying renal capsule and to angiotensin II. Thus angiotensin II apparently plays a primarily homeostatic role in renovascular hypertension to maintain glomerular ultrafiltration. It is suggested that the angiotensin II may be formed intrarenally and may act on sites other than resistance blood vessels.

Pathogenesis of Arterial Hypertension after the Constriction of the Renal Artery Leaving the opposite Kidney Intact Both in the Anaesthetized and in the Conscious Dog

1972 ◽  
Vol 42 (6) ◽  
pp. 651-664 ◽  
Author(s):  
G. Bianchi ◽  
E. Baldoli ◽  
R. Lucca ◽  
P. Barbin
Keyword(s):  
Blood Pressure ◽  
Renal Artery ◽  
Plasma Volume ◽  
Total Peripheral Resistance ◽  
Peripheral Resistance ◽  
Extracellular Fluid ◽  
Plasma Renin ◽  
Conscious Dogs ◽  
Plasma Renin Concentration ◽  
Renal Artery Constriction

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.

scholarly journals Renovascular hypertension using a modified two-kidney, one-clip approach in mice is not dependent on the α1 or α2 Na-K-ATPase ouabain-binding site

2011 ◽  
Vol 301 (3) ◽  
pp. F615-F621 ◽  
Author(s):  
John N. Lorenz ◽  
Valerie M. Lasko ◽  
Michelle L. Nieman ◽  
Thomas Damhoff ◽  
Vikram Prasad ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Renal Artery ◽  
Binding Site ◽  
Renovascular Hypertension ◽  
Plasma Renin ◽  
Mutant Mice ◽  
Ouabain Binding ◽  
Α Subunit ◽  
Pressure Changes ◽  
2K1c Hypertension

Endogenous cardiotonic steroids, through their interaction with the ouabain-binding site of the Na-K-ATPase α-subunit, have been implicated in a variety of cardiovascular disease states including hypertension. We have previously shown that ACTH-induced hypertension is abolished in mutant mice expressing ouabain-resistant α1- and α2-subunits. To further evaluate hypertension resistance in these mutant mice, we examined blood pressure changes in a modified model of 2-kidney, 1-clip (2K1C) renovascular hypertension. To reliably generate 2K1C hypertension, we used polyvinyl tubing (inner diameter: ∼0.27 mm) to accurately gauge the degree of renal artery stenosis. Using this method, virtually all of the clipped mice became hypertensive and there was no incidence of apparent renal ischemia. By telemetry, in response to renal artery clipping, blood pressure in wild-type mice (α1 ouabain-resistant, α2 ouabain-sensitive) increased from 97 ± 3 to 136 ± 7 mmHg. In α1-resistant, α2-resistant mice, pressure increased from 93 ± 2 to 123 ± 4 mmHg, and in α1-sensitive, α2-resistant mice, blood pressure increased from 95 ± 2 to 139 ± 5 mmHg. Blood pressure changes were equivalent in all three groups. In sham mice, blood pressure did not change (96 ± 1 to 95 ± 2 mmHg). Renin mRNA expression was dramatically elevated in the left vs. the right kidney, and plasma renin concentration was elevated similarly in all genotypes. These data indicate that sensitivity of the α1- or α2-Na-K-ATPase binding site to cardiotonic steroids is not a prerequisite for the development of 2K1C renovascular hypertension. In addition, use of a polyurethane cuff to constrict the renal artery provides a reliable method for producing 2K1C hypertension in mice.

Pressor Responsiveness to Angiotensin in Renovascular and Steroid Hypertension

1979 ◽  
Vol 57 (s5) ◽  
pp. 47s-50s ◽  
Author(s):  
E. S. Marks ◽  
H. Thurston ◽  
R. F. Bing ◽  
J. D. Swales
Keyword(s):  
Angiotensin Ii ◽  
Pressor Response ◽  
Plasma Renin ◽  
Receptor Occupancy ◽  
Bilateral Nephrectomy ◽  
Hypertensive Rats ◽  
Response Curves ◽  
Pressor Responses ◽  
Salt Hypertension ◽  
Converting Enzyme Inhibition

1. The pressor response to angiotensin II was reduced in rats with early (&lt;6 weeks) and chronic (&gt;4 months) Goldblatt two-kidney, one-clip hypertension and enhanced in DOCA—salt hypertension. 2. Converting enzyme inhibition with captopril brought the angiotensin pressor response curves into closer proximity although the DOCA hypertensive rats were minimally hyper-responsive and rats with early and chronic renovascular hypertension showed slightly reduced responsiveness. 3. After bilateral nephrectomy the pressor responses to angiotensin were similar. 4. The pressor response to angiotensin II in these animals was inversely related to plasma renin concentration and therefore largely dependent upon receptor occupancy by endogenous angiotensin II. There is no evidence for enhanced pressor responsiveness to angiotensin in either renovascular or DOCA hypertension.

Role of angiotensin II in experimental renal hypertension in the rabbit

1975 ◽  
Vol 228 (1) ◽  
pp. 11-16 ◽  
Author(s):  
JA Johnson ◽  
JO Davis ◽  
B Braverman
Keyword(s):  
Angiotensin Ii ◽  
Arterial Pressure ◽  
Renal Artery ◽  
Renal Hypertension ◽  
Plasma Renin ◽  
Control Group ◽  
Left Renal Artery ◽  
Chronic Hypertension ◽  
Group Of Seven

Hypertension was produced in rabbits by constricting the left renal artery; in nine rabbits the opposite kidney was removed and in eight rabbits the opposite kidney was left intact. To investigate the role of angiotensin II (A-II), 1-sarcosine-8-alanine angiotensin II, a competitive antagonist of A-II, was infused at 6 mug/min per kg body wt for 30 min. In a control group of seven unilaterally nephrectomized rabbits mean arterial pressure averaged 81 mmHg and infusion of the A-II antagonist did not alter the arterial pressure. In a group of Na-depleted rabbits, arterial pressure decreased from 81 to 63 mmHg (P less than 0.01) in response to the A-II analogue. Thirty days after renal artery constriction, seven of the nine one-kidney hypertensive rabbits had normal values for plasma renin activity (PRA) and during infusion of the A-II antagonist arterial pressure was unchanged. However, two rabbits had elevated PRA and the arterial pressure decreased during infusion of the angiotension analogue. In the two-kidney hypertensive rabbits, PRA was normal and arterial pressure was unchanged by infusion of the A-II antagonist. These studies provide evidence that hypertension developed with either a high or normal A-II plasma level in the one-kidney animals; the two-kidney rabbits developed chronic hypertension in which no role for A-II could be demonstrated.

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