Measurement of Renin Activity, Concentration and Substrate in Rat Plasma by Radioimmunoassay of Angiotensin I

Ménard, Joël; Catt, Kevin J.

doi:10.1210/endo-90-2-422

Cited by 475 publications

(178 citation statements)

References 19 publications

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“…Blood was drawn from the right ventricular cavity for plasma renin activity measurement, 14 and the rats were perfusion-fixed with 4% gultaraldehyde in Hanks' solution at 100 mm Hg. The LV was carefully isolated, weighed, embedded in paraffin, and cut into 5-m cross sections.…”

Section: Tissue Preparation and Morphometrymentioning

confidence: 99%

Transforming Growth Factor-β Function Blocking Prevents Myocardial Fibrosis and Diastolic Dysfunction in Pressure-Overloaded Rats

et al. 2002

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Background-Excessive myocardial fibrosis impairs cardiac function in hypertensive hearts. Roles of transforming growth factor (TGF)-␤ in myocardial remodeling and cardiac dysfunction were examined in pressure-overloaded rats. Methods and Results-Pressure overload was induced by a suprarenal aortic constriction in Wistar rats. Fibroblast activation (proliferation and phenotype transition to myofibroblasts) was observed after day 3 and peaked at days 3 to 7. Thereafter, myocyte hypertrophy and myocardial fibrosis developed by day 28. At day 28, echocardiography showed normal left ventricular fractional shortening, but the decreased ratio of early to late filling velocity of the transmitral Doppler velocity and hemodynamic measurement revealed left ventricular end-diastolic pressure elevation, indicating normal systolic but abnormal diastolic function. Myocardial TGF-␤ mRNA expression was induced after day 3, peaked at day 7, and remained modestly increased at day 28. An anti-TGF-␤ neutralizing antibody, which was administered intraperitoneally daily from 1 day before operation, inhibited fibroblast activation and subsequently prevented collagen mRNA induction and myocardial fibrosis, but not myocyte hypertrophy. Neutralizing antibody reversed diastolic dysfunction without affecting blood pressure and systolic function. Conclusions-TGF-␤ plays a causal role in myocardial fibrosis and diastolic dysfunction through fibroblast activation in pressure-overloaded hearts. Our findings may provide an insight into a new therapeutic strategy to prevent myocardial fibrosis and diastolic dysfunction in pressure-overloaded hearts.

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Section: Tissue Preparation and Morphometrymentioning

confidence: 99%

Transforming Growth Factor-β Function Blocking Prevents Myocardial Fibrosis and Diastolic Dysfunction in Pressure-Overloaded Rats

et al. 2002

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“…16 Plasma (20 fiL) was incubated at pH 7.4 and 37°C with an excess of angiotensinogen (50 /iL of renin-free rat plasma), and the angiotensin I formed was measured by radioimmunoassay.…”

Section: Plasma Renin Concentrationmentioning

confidence: 99%

Kidney is an important target for the antihypertensive action of an angiotensin II receptor antagonist in spontaneously hypertensive rats.

1993

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Inhibitors of the renin-angiotensin system lower blood pressure of spontaneously hypertensive rats, although plasma renin is not elevated. To test the hypothesis that the actions of angiotensin II within the kidney may contribute to the high blood pressure in spontaneously hypertensive rats, we infused valsartan, a subtype 1 angiotensin II receptor antagonist, via the suprarenal artery into the right kidney of conscious, freely moving, unilaterally nephrectomized (left) spontaneously hypertensive rats (12 to 14 weeks old). Valsartan (03 mg/kg per day for 48 hours) lowered blood pressure (change in blood pressure, -7 ± 3 , -1 9 ± 4 , and -2 6 ± 4 mm Hg, n = l l , at 12, 24, and 48 hours) after intrarenal administration but had no significant effect on blood pressure after intravenous administration (change in blood pressure, 1±5, -3 ± 4 , and 10±5 mm Hg, n=l, at 12, 24, and 48 hours). Infusion of vehicle (0.9% saline) intrarenally had no significant effect on blood pressure (change in blood pressure, 2±5, -1 ± 6 , and 0±7 mm Hg, n = l l , at 12, 24, and 48 hours). The maximum fall in blood pressure reached after intrarenal administration of this dose of valsartan was similar to the maximum fall induced after intravenous administration of higher doses (change in blood pressure, -1 4 ± 5 , -27±4, and -3 2 ± 5 mm Hg, n=7, at 12,24, and 48 hours after 3 mg/kg per day i.v.). Thus, endogenous angiotensin II acting within the kidney appears to play an important role in the maintenance of high blood pressure in spontaneously hypertensive rats. Renal function studies have shown that renal hemodynamic abnormalities may be involved in the initiation of hypertension in SHR. Young SHR (4 to 6 weeks) are moderately hypertensive and have a reduced glomerular filtration rate and renal blood flow and an increased renal vascular resistance compared with the normotensive Wistar-Kyoto control strain. 2 -3 Moreover, an exaggerated salt and water retention has been detected in young SHR. 2 As the hypertension develops, renal hemodynamic abnormalities become normalized (after 12 to 14 weeks of age). The low renal blood flow and glomerular filtration rate in young SHR may be a stimulus for BP to increase and return renal perfusion to normal. SHR have a normal to low plasma renin activity 4 -5 and have not generally been considered to be a renindependent model of hypertension. 6 However, the antihypertensive efficacy of renin inhibitors, 7 angiotensin converting enzyme (ACE) inhibitors, 7 " 9 and angiotensin II (Ang II) receptor antagonists 510 in SHR implicates an involvement of the renin-angiotensin system in the pathogenesis of hypertension in this animal model. Treatment of SHR with an ACE inhibitor normalizes glomerular filtration rate, renal blood flow, renal vascular resistance, and BP, 9 suggesting a role for Ang II in both the renal hemodynamic abnormalities and development of hypertension. The observation that the antihypertensive response induced by renin inhibition, ACE inhibition, or Ang II receptor antagonism in SHR is abol...

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“…Plasma insulin levels were determined by radioimmunoassay, using a double antibody technique [15]. Plasma renin concentration was determined as the rate of angiotensin I generation in plasma incubated for 2 h at pH 6.5 in the presence of excess rat angiotensinogen using the method of Menard and Catt [16].…”

Section: Methodsmentioning

confidence: 99%

Effects of angiotensin II on insulin receptor binding and mRNA levels in normal and diabetic rats

et al. 1997

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The observation that hyperinsulinaemia and insulin resistance are present in subjects with essential hypertension has led to the hypothesis that insulin is involved in the pathophysiology of this disease [1][2][3]. When considering possible pathogenetic mechanisms that could mediate the prohypertensive effect of insulin, particular attention has been paid to the renal actions of the hormone. Insulin decreases urinary sodium excretion in rats [4], dogs [5,6], and humans [7, Diabetologia (1997) Summary Both the density and level of mRNA encoding insulin receptors in the kidney are inversely related to the dietary sodium content, suggesting a feedback mechanism that limits the insulin-induced sodium retention when extracellular fluid volume is expanded. Because angiotensin II affects tissue sensitivity to insulin in humans, we investigated whether angiotensin II affects insulin receptor binding and mRNA levels in the kidney, liver, and renal arteries of normal rats and rats with streptozotocin-induced diabetes mellitus. Non-diabetic and diabetic rats were infused for 7 days with either vehicle or angiotensin II at a rate of 200 ng ⋅ kg −1 ⋅ min −1 . In a separate experiment, normal rats were treated with an angiotensin converting enzyme inhibitor (captopril, 100 mg/dl in the drinking water) or vehicle for 7 days. Regional analysis of insulin receptor binding in the kidney and renal arteries was performed by an in situ technique using computerized microdensitometry and emulsion autoradiography. Insulin receptor mRNA levels were determined in renal and hepatic tissue by Northern blot hybridization and normalized with 28S rRNA. No differences in blood pressure were observed among diabetic and non-diabetic rats infused with either vehicle or angiotensin II, whereas captopril-treated rats had significantly lower blood pressure levels than their respective controls. Angiotensin II significantly decreased plasma renin concentration in both non-diabetic and diabetic rats. Insulin receptor number was significantly greater in the renal cortex of diabetic rats than in non-diabetics, whereas no significant differences were found in the outer medulla, inner medulla, or renal arteries. Angiotensin II infusion did not affect either the number or affinity of insulin receptors in any of the renal regions studied. Insulin receptor mRNA levels were significantly greater in the kidney and liver of diabetic rats than in non-diabetics and were not affected by angiotensin II infusion. Similar to angiotensin II infusion, captopril treatment did not affect either renal insulin receptor binding or mRNA levels. Thus, diabetic rats have increased insulin receptor binding and mRNA levels in comparison to non-diabetic rats. Angiotensin II infusion and captopril treatment do not affect insulin receptor binding and mRNA levels in the kidney, arguing against a role for this peptide in the modulation of renal sensitivity to insulin. [Diabetologia (1997) 40: 770-777]

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Measurement of Renin Activity, Concentration and Substrate in Rat Plasma by Radioimmunoassay of Angiotensin I

Cited by 475 publications

References 19 publications

Transforming Growth Factor-β Function Blocking Prevents Myocardial Fibrosis and Diastolic Dysfunction in Pressure-Overloaded Rats

Transforming Growth Factor-β Function Blocking Prevents Myocardial Fibrosis and Diastolic Dysfunction in Pressure-Overloaded Rats

Kidney is an important target for the antihypertensive action of an angiotensin II receptor antagonist in spontaneously hypertensive rats.

Effects of angiotensin II on insulin receptor binding and mRNA levels in normal and diabetic rats

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