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.

Inhibition of angiotensin conversion and prevention of renal hypertension

1975 ◽  
Vol 228 (2) ◽  
pp. 448-453 ◽  
Author(s):  
Miller ED ◽  
AI Samuels ◽  
E Haber ◽  
AC Barger
Keyword(s):  
Blood Pressure ◽  
Renal Artery ◽  
Renovascular Hypertension ◽  
Renal Hypertension ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Renin Activity ◽  
Angiotensin System ◽  
The One ◽  
Renal Artery Constriction

Renal artery constriction in the unilaterally nephrectomized, trained dog, with maintained renal arterial hypotension, produces a prompt increase in systemic renin activity and blood pressure. The hypertension normally induced by renal artery stenosis is prevented by prior treatment with the nonapeptide Pyr-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro (SQ 20, 881), which blocks conversion of angiotensin I to angiotensin II. Constant intravenous infusion of the inhibitor over several days of renal artery constriction prevents the development of chronic renovascular hypertension. Furthermore, a single injection of the nonapeptide restores blood pressure to normal in the early phase of renovascular hypertension, but becomes progressively less effective as salt and water retention occurs in the chronic stage when plasma renin activity returns to control levels. These data provide strong evidence that the renin-angiotensin system is responsible for the initiation of renovascular hypertension in the one-kidney Goldblatt dog, but that other factors become increasingly important in chronic renovascular hypertension.

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.

Renovascular Hypertension with Low-to-Normal Plasma Renin: Clinical and Angiographic Features

1997 ◽  
Vol 93 (5) ◽  
pp. 435-443 ◽  
Author(s):  
Gian Paolo Rossi ◽  
Edoardo Pavan ◽  
Matteo Chiesura-Corona ◽  
Michael Bader ◽  
Giovanni Paganini ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Renal Artery ◽  
Renovascular Hypertension ◽  
Renal Vein ◽  
Plasma Renin ◽  
Artery Occlusion ◽  
Total Occlusion ◽  
Renal Ischaemia ◽  
Renal Vein Renin ◽  
Artery Obstruction

1. Low-to-normal renin renovascular hypertension (RVH) and the accuracy of renal vein renin ratios were investigated in 129 consecutive patients referred for suspected RVH. Forty-nine had essential hypertension, 24 unilateral renoparenchymal hypertension and 56 renal artery obstruction. Of the latter, 86% were diagnosed retrospectively as RVH, based on fall in blood pressure with correction of renal ischaemia. We measured baseline, captopril-stimulated and renal vein plasma renin activity (PRA) levels, as well as several other parameters. 2. PRA was low-to-normal in 37% of the RVH patients [low-to-normal renin (LNR-) RVH group] and elevated in the remaining 63% [high-renin (HR-) RVH group]. In the LNR-RVH group, low-to-normal renin levels, by immunoreactive active renin and plasma renin concentration measurements, and a blunted response of PRA to captopril, were seen. As compared with HR-RVH, LNR-RVH patients had a longer duration of hypertension (P < 0.05), higher serum K+ (P = 0.04) and lower diastolic blood pressure (P = 0.02). However, they did not differ for the other variables, including the fall in blood pressure after correction of renal ischaemia. Although the number of bilateral stenoses was similar in the two groups, no patient in the LNR-RVH group had total renal artery occlusion compared with 53% in the HR-RVH group (P = 0.00015). The accuracy of renal vein renin indices were high enough to justify their use only in the patients with total occlusion of a renal artery. 3. Thus LNR-RVH is common in patients with longstanding hypertension without a totally occluded renal artery. Since the sensitivity of renin measurements is low, cure of hypertension would be precluded for more than one third of RVH patients, if these tests were a prerequisite for identifying RVH.

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.

Thromboxane A2-prostaglandin H2 and renovascular hypertension in rats

1994 ◽  
Vol 267 (5) ◽  
pp. R1190-R1197 ◽  
Author(s):  
E. H. Boussairi ◽  
J. Sacquet ◽  
J. Sassard ◽  
D. Benzoni
Keyword(s):  
Blood Pressure ◽  
Renal Artery ◽  
Receptor Antagonist ◽  
Renovascular Hypertension ◽  
Vascular Reactivity ◽  
Thromboxane A2 ◽  
Malignant Hypertension ◽  
Receptor Blockade ◽  
Vascular Responsiveness ◽  
Goldblatt Hypertension

To evaluate the contribution of thromboxane (Tx) A2-prostaglandin (PG) H2 in two-kidney, one-clip Goldblatt hypertension (GH), 26 GH rats were chronically treated (GHT) with a specific TxA2-PGH2 receptor antagonist, CGS-22652 (30 mg.kg-1.24 h-1 sc); 28 others as well as 17 sham-clipped (SC) rats received vehicle. Twelve GH and 3 GHT rats developed malignant hypertension and died. After 6 wk of treatment, GH rats exhibited higher mean blood pressure (BP; 189 +/- 3 vs. 118 +/- 2 mmHg) and an increased vascular reactivity to the main pressor agents compared with SC rats. Chronic TxA2-PGH2 receptor blockade lowered mean BP in 13 GHT rats (125 +/- 3 mmHg) and decreased their vascular reactivity compared with GH rats. However, 10 GHT rats remained hypertensive (190 +/- 9 mmHg) and differed from the former by an increased vascular reactivity to vasopressin. It is concluded that renal artery clipping induces either benign or malignant hypertension. In benign forms, TxA2-PGH2 blockade normalizes BP through decreasing the vascular responsiveness to the main pressor agents. In malignant forms, it limits the elevation of BP and markedly reduces mortality.

Contribution of Stenosis Resistance to the Rise in total Peripheral Resistance during Experimental Renal Hypertension in Conscious Dogs

1981 ◽  
Vol 61 (6) ◽  
pp. 663-670 ◽  
Author(s):  
W. P. Anderson ◽  
P. I. Korner ◽  
J. A. Angus ◽  
C. I. Johnston
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Cardiac Output ◽  
Plasma Renin Activity ◽  
Renal Artery ◽  
Total Peripheral Resistance ◽  
Peripheral Resistance ◽  
Plasma Renin ◽  
Vascular Beds ◽  
Renal Vascular

1. Mild, moderate and severe renal artery stenosis was induced in uninephrectomized conscious dogs by inflating a renal artery cuff to lower distal pressure to 60, 40 or 20 mmHg respectively. The renal artery was narrowed progressively over the next 3 days by further inflation of the cuff to relower the distal renal artery pressure to the initial values. 2. Graded progressive stenosis produced graded progressive rises in blood pressure, plasma renin activity and total renal resistance to flow over the 3 day period, followed by a return to control values 24 h after cuff deflation. 3. The rise in total renal resistance to flow was almost entirely due to the stenosis, with only small changes occurring in renal vascular resistance. 4. in moderate and severe stenosis cardiac output did not alter significantly and thus increases in blood pressure were due to increases in total peripheral resistance. in these groups the resistance to blood flow of the stenosis accounted respectively for about 36 and 26% of the rises in total peripheral resistance. Vasoconstriction of the other non-renal vascular beds accounted for the remainder of the increase in total peripheral resistance. 5. in mild stenosis the changes in both cardiac output and total peripheral resistance were variable and not statistically significant. in this group the rise in stenosis resistance was compensated by vasodilatation of the non-renal vascular beds. 6. in all groups rises in plasma renin activity and blood pressure correlated with the haemodynamic severity of the stenosis. 7. Thus the resistance to blood flow of the moderate and severe renal artery stenoses accounted for one-quarter to one-third of the increases in total peripheral resistance. The remainder of the increase in total peripheral resistance was due to vasoconstriction of nonrenal beds.

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.

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.

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