Sex and age differences of renal function in rats with reduced ANG II activity during the nephrogenic period

2007 ◽  
Vol 293 (2) ◽  
pp. F506-F510 ◽  
Author(s):  
Analia Loria ◽  
Virginia Reverte ◽  
Francisco Salazar ◽  
Fara Saez ◽  
M. Teresa Llinas ◽  
...  

This study was designed to test the hypothesis that blockade of angiotensin II effects during renal development accelerates the aging-related changes in renal hemodynamics and proteinuria, and that these changes are sex dependent. It has also been examined whether the deterioration of urinary concentrating ability elicited by angiotensin II blockade is sex and/or aging dependent. Newborn Sprague-Dawley rats were treated with vehicle or an AT1 angiotensin II receptor antagonist (ARA) during the first 14 postnatal days. Blood pressure, glomerular filtration rate, proteinuria, and urinary concentrating ability in response to dehydration were examined in conscious rats at 3 and 11 mo of age. ARA treatment elicited a similar increment in blood pressure in males and females that was greater ( P < 0.05) at 11 than at 3 mo of age. Glomerular filtration rate only decreased ( P < 0.05) in 11-mo-old male ARA-treated rats (0.59 ± 0.07 vs. 0.80 ± 0.07 ml·min−1·g−1 in control group). At 3 mo of age, proteinuria increased in male (107%) but not in female ARA-treated rats. However, at 11 mo of age, proteinuria increased in both sexes, but the increment was greater ( P < 0.05) in male (244%) than in female (138%) ARA-treated rats. Renal ability to concentrate urine in response to prolonged water dehydration was only reduced in ARA-treated males. The reduction of urinary concentrating ability was accentuated by aging. Therefore, we conclude that blockade of angiotensin II effects during renal development elicits an important deterioration of cortical and medullary function that is sex and aging dependent.

2013 ◽  
Vol 304 (7) ◽  
pp. F900-F907 ◽  
Author(s):  
Norma B. Ojeda ◽  
Thomas P. Royals ◽  
Barbara T. Alexander

This study tested the hypothesis that Rho kinase contributes to the enhanced pressor response to acute angiotensin II in intact male growth-restricted and gonadectomized female growth-restricted rats. Mean arterial pressure (MAP) and renal function were determined in conscious animals pretreated with enalapril (250 mg/l in drinking water) for 1 wk to block the endogenous renin-angiotensin system and normalize blood pressure (baseline). Blood pressure and renal hemodynamics did not differ at baseline. Acute Ang II (100 ng·kg−1·min−1) induced a greater increase in MAP and renal vascular resistance and enhanced reduction in glomerular filtration rate in intact male growth-restricted rats compared with intact male controls ( P < 0.05). Cotreatment with the Rho kinase inhibitor fasudil (33 μg·kg−1·min−1) significantly attenuated these hemodynamic changes ( P < 0.05), but it did not abolish the differential increase in blood pressure above baseline, suggesting that the impact of intrauterine growth restriction on blood pressure in intact male growth-restricted rats is independent of Rho kinase. Gonadectomy in conjunction with fasudil returned blood pressure back to baseline in male growth-restricted rats, and yet glomerular filtration rate remained significantly reduced ( P < 0.05). Thus, these data suggest a role for enhanced renal sensitivity to acute Ang II in the developmental programming of hypertension in male growth-restricted rats. However, inhibition of Rho kinase had no effect on the basal or enhanced increase in blood pressure induced by acute Ang II in the gonadectomized female growth-restricted rat. Therefore, these studies suggest that Rho kinase inhibition exerts a sex-specific effect on blood pressure sensitivity to acute Ang II in growth-restricted rats.


1998 ◽  
Vol 84 (6) ◽  
pp. 2154-2162 ◽  
Author(s):  
Cord Sturgeon ◽  
Albert D. Sam ◽  
William R. Law

Rapid measurement of glomerular filtration rate (GFR) by an inulin single-bolus technique would be useful, but its accuracy has been questioned. We hypothesized that reported inaccuracies reflect the use of inappropriate mathematical models. GFR was measured in 14 intact and 5 unilaterally nephrectomized conscious male Sprague-Dawley rats (mean weight 368 ± 12 g) by both single-bolus (25 mg/kg) and constant-infusion techniques (0.693 mg ⋅ kg−1 ⋅ min−1). The temporal decline in plasma inulin concentration was analyzed through biexponential curve fitting, which accounted for renal inulin loss before complete vascular and interstitial mixing. We compared our mathematical model based on empirical rationale with those of other investigators whose studies suggest inaccuracy of single-bolus methods. Our mathematical model yielded GFR values by single bolus that agreed with those obtained by constant infusion [slope = 0.94 ± 0.16 (SE); y intercept = 0.23 ± 0.64; r = 0.82]. In comparison to the data obtained by constant inulin infusion, this method yielded a very small bias of −0.0041 ± 0.19 ml/min. Two previously reported models yielded unsatisfactory values (slope = 1.46 ± 0.34, y intercept = 0.47 ± 1.5, r = 0.72; and slope = 0.17 ± 1.26, y intercept = 17.15 ± 5.14, r = 0.03). The biases obtained by using these methods were −2.21 ± 0.42 and −13.90 ± 1.44 ml/min, respectively. The data indicate that when appropriate mathematical models are used, inulin clearance after single-bolus delivery can be used to measure GFR equivalent to that obtained by constant infusion of inulin. Attempts to use methods of analysis for simplicity or expediency can result in unacceptable measurements relative to the clinical range of values seen.


1975 ◽  
Vol 49 (3) ◽  
pp. 193-200 ◽  
Author(s):  
C. H. Espinel

1. The influence of dietary sodium intake on the glomerular filtration rate (GFR/nephron) and potassium and phosphate excretion was examined at three stages of progressive chronic renal failure produced in rats by sequential partial nephrectomies. 2. The adaptive increased sodium excretion per nephron in the control group receiving a constant sodium intake did not occur in the experimental group that had a gradual reduction of dietary sodium in direct proportion to the fall in GFR. 3. Despite the difference in sodium excretion, the increase in GFR/nephron, the daily variation in the amount of potassium and phosphate excreted, the increase in potassium and phosphate excretion per unit nephron, and the plasma potassium and phosphate concentrations were the same in the two groups. 4. The concept of ‘autonomous adaptation’ in chronic renal failure is presented.


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