Glomerular injury in uninephrectomized spontaneously hypertensive rats. A consequence of glomerular capillary hypertension.

Dworkin, Lance D.; Feiner, Helen

doi:10.1172/jci112377

Cited by 185 publications

(84 citation statements)

References 38 publications

(37 reference statements)

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“…28 The development of diabetic renal injury was accelerated by uninephrectomy, which has been shown to increase glomerular capillary hydraulic pressure and plasma flow rate in nondiabetic rats. 29 This study confirmed that in SHR a high salt intake prevents the hypotensive effect of chronic ACE inhibitor therapy. 1617 Treatment with ramipril produced a fall in systemic systolic blood pressure only when administered to rats receiving a normal salt intake.…”

Section: Discussionsupporting

confidence: 78%

Salt blocks the renal benefits of ramipril in diabetic hypertensive rats.

1991

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To establish if the benefit of angiotensin converting enzyme inhibitor therapy in retarding progressive diabetic renal injury is due to a specific intrarenal effect or the systemic hypotensive effect, we studied the effect of long-term ramipril treatment on blood pressure, glomerular filtration rate, and urinary protein excretion in streptozotocin-diabetic spontaneously hypertensive rats. The hypotensive effect of ramipril was prevented by a high salt diet, which did not alter the degree of renal angiotensin converting enzyme inhibition. Three weeks after uninephrectomy and induction of diabetes, rats were allocated to three groups. Groups 1 and 2 were given 1% NaCl, whereas group 3 was given water as drinking solution. One week later, groups 2 and 3 received 0.4 mg/kg/day ramipril in their drinking solution, which was continued over a 2-month period. Ramipril produced a blood pressure fall only in water-drinking rats (group 3) despite a similar reduction in plasma and renal angiotensin converting enzyme activity in groups 2 and 3. Salt-loaded rats had a progressive increase in urinary protein excretion over the duration of study. Ramipril treatment prevented an increase in protein excretion only in animals given water and with a reduced systolic blood pressure. Glomerular nitration rate was similar in all three groups. Ramipril treatment improved animal survival independently of a reduction in blood pressure or an effect on proteinuria. Although it is possible that angiotensin converting enzyme inhibitors have specific intrarenal effects reducing progression of diabetic proteinuria, concomitant control of systemic blood pressure appears to be necessary to demonstrate a benefit. (Hypertension 1991;17:497-503) U ncontrolled systemic hypertension is a wellknown cause of progressive renal injury in both humans and experimental animals. 1Hypertension is commonly associated with diabetic renal disease,'-3 and it has been shown to accelerate the rate of development of diabetic nephropathy both in humans 4 and in streptozotocin-diabetic rats. 13 or in other renal disorders. 1415 However, it is difficult to determine from these studies if the beneficial effect of ACE Received February 9, 1990; accepted in revised form November 29, 1990. inhibitors was due to a specific intrarenal effect of ACE inhibition or due to their systemic hypotensive effect.To evaluate this question further, we examined the effect of long-term administration of the ACE inhibitor ramipril on blood pressure, glomerular filtration rate, and proteinuria in streptozotocin diabetic uninephrectomized spontaneously hypertensive rats (SHR). To prevent the hypotensive effect of ACE inhibition, the rats were maintained on a high salt diet, which is known to oppose the blood pressurelowering action of ACE inhibitors. -17 Methods Study Protocol

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Section: Discussionsupporting

confidence: 78%

Salt blocks the renal benefits of ramipril in diabetic hypertensive rats.

1991

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“…In the previous experimental studies in different hypertensive models, it was found that increased glomerular pressure might be involved in the development of glomerulosclerosis which was associated with a compensatory glomerular hyperfiltration [4,5,18]. In this study, we observed that the systolic blood pressure of FGS/Nga was slightly higher than CBA/N and RFM/ Nga mice.…”

Section: Discussionsupporting

confidence: 53%

Changes of Renal Lesion-Related Parameters in FGS/Nga and the Parental Mouse Strains, CBA/N and RFM/Nga.

Kim

Choi²,

Lee

et al. 2004

Exp. Anim.

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Abstract:The FGS/Nga mouse strain, established from an outcross between CBA/N and RFM/Nga mice strains, has previously been reported as a spontaneous mouse model for focal glomerular sclerosis (FGS) and is considered to have two pairs of autosomal recessive genes associated with FGS. In this study, we examined the changes of seven renal lesion-related parameters, blood urea nitrogen (BUN), creatinine, albumin and total protein in plasma, urinary protein, systolic blood pressure, and a glomerulosclerosis index on histological observation, in 20-week-old FGS/Nga mice and their age-matched two parental strains, CBA/N and RFM/Nga. The levels of plasma BUN and creatinine, urinary protein and systolic blood pressure were significantly increased in FGS/Nga, compared with those of the parental strains. RFM/Nga mice showed slightly elevated levels of all biochemical makers. In histological analysis, a higher glomerulosclerosis index was observed in FGS/Nga than the two parental strains. RFM/Nga mice appeared to have slight sclerotic lesions of glomeruli, but no renal failure was observed in CBA/N mice. These results suggest that at least one mutant gene that causes the progression of renal lesion in FGS/Nga mice is derived from RFM/Nga. Key words: animal model, focal glomerular sclerosis (FGS), mouse, proteinuria function in human renal diseases [9,17]. Although it has been demonstrated by previous studies that the development of FGS is involved in immunologic injury, hemodynamic injury and metabolic abnormalities [1,6,7,10], the precise pathogenesis of FGS is still unclear.The FGS/Nga strain of mouse was introduced to

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“…This action could provide reverse glomerular capillary hypertension and additional amelioration of renal injury. 27,28 To assess this possibility of bradykinin-induced renal protection, we simultaneously administered the bradykinin antagonist icatibant (HOE140) with enalapril. However, the icatibant (HOE140) only blunted the systemic antihypertensive effects of enalapril and failed to attenuate the enalapril-induced effects of renoprotection and the progression of glomerulosclerosis.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin Type 1 Receptor Antagonism and ACE Inhibition Produce Similar Renoprotection in N ^ω -Nitro- l >-Arginine Methyl Ester/Spontaneously Hypertensive Rats

et al. 2001

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Abstract-This study was conducted to determine potentially differential effects between an angiotensin II type 1 (AT 1 ) receptor antagonist and an ACE inhibitor on systemic, renal, and glomerular hemodynamics and pathological changes in spontaneously hypertensive rats (SHR) with N -nitro-L-arginine methyl ester (L-NAME)-exacerbated nephrosclerosis. The hemodynamic, renal micropuncture, and pathological studies were performed in 9 groups of 17-week-old male SHR treated as follows: group 1, controls (nϭ16); group 2, candesartan (10 mg/kg per day for 3 weeks) (nϭ7); group 3, enalapril (30 mg/kg per day for 3 weeks) (nϭ8); group 4, candesartan (5 mg/kg per day) plus enalapril (15 mg/kg per day for 3 weeks) (nϭ9); group 5, L-NAME (50 mg/L in drinking water for 3 weeks) (nϭ17); group 6, L-NAME (50 mg/L) plus candesartan (10 mg/kg per day for 3 weeks) (nϭ7); group 7, L-NAME (50 mg/L) for 3 weeks followed by candesartan (10 mg/kg per day) for another 3 weeks (nϭ8); group 8, L-NAME (50 mg/L) plus enalapril (30 mg/kg per day for 3 weeks) (nϭ7); and group 9, L-NAME (50 mg/L) plus enalapril (30 mg/kg per day) and the bradykinin antagonist icatibant (500 g/kg SC per day via osmotic minipump for 3 weeks) (nϭ7). Both candesartan and enalapril similarly reduced mean arterial pressure and total peripheral resistance index. These changes were associated with significant decreases in afferent and efferent glomerular arteriolar resistances as well as glomerular capillary pressure. Histopathologically, the glomerular and arterial injury scores were decreased significantly, and left ventricular and aortic masses also were diminished significantly in all treated groups. L-NAME-induced urinary protein excretion was prevented by both candesartan and enalapril. Thus, both AT 1 receptor and ACE inhibition prevented and reversed the pathophysiological alterations of L-NAME-exacerbated nephrosclerosis in SHR. Itatibant only blunted the antihypertensive effects of enalapril but did not attenuate the beneficial effects of ACE inhibition on the L-NAME-induced nephrosclerosis. Thus, the AT 1 receptor antagonism and ACE inhibition have similar renal preventive effects, which most likely were achieved through reduction in the effects of angiotensin II, and ACE inhibition of bradykinin degradation demonstrated little evidence of renoprotection. (Hypertension. 2001;37:1262-1267.)

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Glomerular injury in uninephrectomized spontaneously hypertensive rats. A consequence of glomerular capillary hypertension.

Cited by 185 publications

References 38 publications

Salt blocks the renal benefits of ramipril in diabetic hypertensive rats.

Salt blocks the renal benefits of ramipril in diabetic hypertensive rats.

Changes of Renal Lesion-Related Parameters in FGS/Nga and the Parental Mouse Strains, CBA/N and RFM/Nga.

Angiotensin Type 1 Receptor Antagonism and ACE Inhibition Produce Similar Renoprotection in N ^ω -Nitro- l >-Arginine Methyl Ester/Spontaneously Hypertensive Rats

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Glomerular injury in uninephrectomized spontaneously hypertensive rats. A consequence of glomerular capillary hypertension.

Cited by 185 publications

References 38 publications

Salt blocks the renal benefits of ramipril in diabetic hypertensive rats.

Salt blocks the renal benefits of ramipril in diabetic hypertensive rats.

Changes of Renal Lesion-Related Parameters in FGS/Nga and the Parental Mouse Strains, CBA/N and RFM/Nga.

Angiotensin Type 1 Receptor Antagonism and ACE Inhibition Produce Similar Renoprotection in N ω -Nitro- l >-Arginine Methyl Ester/Spontaneously Hypertensive Rats

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Angiotensin Type 1 Receptor Antagonism and ACE Inhibition Produce Similar Renoprotection in N ^ω -Nitro- l >-Arginine Methyl Ester/Spontaneously Hypertensive Rats