Plasma Renin Activity Decrease Precedes Spontaneous Focal Glomerular Sclerosis in Aging Rats

Magro, Albert M.; Rudofsky, Ulrich H.

doi:10.1159/000182654

Cited by 32 publications

(8 citation statements)

References 13 publications

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“…Interestingly, Reckelhoff et al (39) did not observe elevated basal or hypertonic saline-stimulated plasma ANP levels in aged SD rats, and aged rats of this strain do not show impaired drinking responses to hypertonic saline treatment (12). As ANP can have inhibitory effects in the rat on dehydrational and Ang II-induced drinking (20), it is possible that the high levels of ANP in aged MW rats are the cause of the reduced drinking in response to systemic hypertonicity.…”

Section: Discussionmentioning

confidence: 91%

“…There is evidence that the renin-Ang system becomes depressed in aged rats and humans (19,20,34), suggesting that this factor could be a cause of the depressed water intake in aged MW rats, in response to both PEG-induced hypovolemia and dehydration. However, isoproterenol-induced drinking, which depends on endogenous Ang II formation (27), was not significantly reduced in old rats, suggesting that in the MW rat strain, reduced activity of the renin-Ang system is not a major factor in depressed drinking responses.…”

Section: Discussionmentioning

confidence: 99%

“…and C.J.T., unpublished data). As well, most strains of rats examined show a depressed activity of the renin angiotensin (Ang) system as they age (19,20). Each of these factors may influence thirst and water intake in rats (21)(22)(23) and humans (7,(24)(25)(26).…”

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confidence: 99%

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Differential effects of aging on fluid intake in response to hypovolemia, hypertonicity, and hormonal stimuli in Munich Wistar rats

Denton

Thomas

Woods

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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A significant proportion of aged humans may have impaired thirst and inadequate fluid intake after a period of fluid deprivation. We have studied the water drinking responses, relative to body weight, of Munich Wistar (MW) rats in response to osmotic, hypovolemic, dehydrational, and angiotensin (Ang)-related stimuli as they aged from 3 to 24 months. Young 3-months-old (m.o.) rats had the largest daily fluid intakes and drinking responses to hypertonic and dehydrational stimuli, suggesting that they have accentuated thirst in comparison with older age groups. There were no differences in daily fluid intake from 6 -24 m.o.; however, drinking responses to i.p. injection of hypertonic 0.4 mol͞liter NaCl gradually declined over this period so that in 24-m.o. rats the response was only half that of 6-m.o. rats. Water intake after 24-h water deprivation also declined gradually over 24 months. Drinking responses to hypovolemia induced by s.c. injection of colloid (polyethylene glycol) were unchanged in 6-to 15-m.o. rats, then declined precipitously in 18-to 24-m.o. rats. Drinking responses to s.c. Ang II or s.c. isoproterenol were not reduced in 24-m.o. rats, nor was the drinking associated with feeding. Therefore, there are specific impairments of water intake in response to hypertonicity and hypovolemia in aged MW rats, but Ang-related drinking is not reduced. Like aged humans, aged MW rats exhibit high plasma atrial natriuretic peptide levels and impaired cardiovascular reflexes that could contribute to the impairment of thirst with age.thirst ͉ osmoregulation ͉ angiotensin ͉ age ͉ dehydration A dequate water intake is essential for life in most mammals. Thirst provides a specific motivational stimulus to ingest fluids when bodily fluid water content falls or its tonicity rises. Thus, factors that impair the thirst mechanism can have severe deleterious effects, leading to dehydration and even death. A significant proportion of aged human subjects has an impairment of thirst, particularly after a period of fluid deprivation (1, 2). Thus, they may be at risk for dehydration and in conditions of hot weather become severely dehydrated and at risk for heat stroke and circulatory collapse (3).Whether thirst in general is reduced in aged humans, or there is a specific deficit in thirst in response to a particular dipsogenic stimulus such as hypertonicity, hypovolemia, or some other factor is unresolved. Fluid deprivation, resulting in dehydration that entails both hypertonicity and hypovolemia of extracellular fluid, usually has resulted in lower thirst ratings in elderly subjects (1, 2, 4-7). However, diminished thirst and reduced water drinking in response to i.v. infusion of hypertonic saline in elderly compared with younger subjects has been reported by some (8, 9) but not all investigators (10, 11). The effect of aging on human thirst in response to hypovolemia per se appears not to have been investigated. Some strains of rats have been surveyed as suitable models for studying the effect of aging on thirst. Aged rats o...

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

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Differential effects of aging on fluid intake in response to hypovolemia, hypertonicity, and hormonal stimuli in Munich Wistar rats

Denton

Thomas

Woods

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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“…17,50 Before the development of hypertension, these animals show glomerular hyperfiltration. 51 Despite the fact that these animals appear to have low plasma renin activity, ACE inhibition 52 or angiotensin receptor blockade 53 restores renal function and BP to normal.…”

Section: Discussionmentioning

confidence: 99%

Glomerular Hyperfiltration, High Renin, and Low- Extracellular Volume in High Blood Pressure

et al. 2000

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Abstract-Abnormal renovascular resistance and glomerular filtration rate are characteristic of established hypertension and may also be involved in its pathogenesis. To determine renal and body fluid correlates of the predisposition to high blood pressure, we examined 100 healthy young adults with high or low blood pressure. Within each group, half had parents with high blood pressures, and half had parents with low blood pressures. Renal function and hemodynamics, body fluid volumes, and relevant hormones and genotypes were measured. Subjects with high personal and parental blood pressures had the highest levels of glomerular filtration rate (PϽ0.02) and plasma active renin concentration and low levels of exchangeable sodium and plasma volume (PϽ0.02). High glomerular filtration rate was not associated with differences in urinary kallikrein or prostaglandins. Polymorphisms of the renin, angiotensin-converting enzyme, and angiotensinogen genes were not associated with differences in glomerular filtration rate or renin. Subjects with high personal, but low parental, blood pressures had low exchangeable sodium and plasma volumes (PϽ0.02) but normal glomerular filtration rates. In this population, extracellular volume depletion and high renin are correlates of high blood pressure in early adulthood, and glomerular hyperfiltration is a feature of those who also have familial predisposition to high blood pressure. (Hypertension. 2000;35:952-957.)

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“…Dear Sir, Focal glomerulosclerosis (FGS) in man is usually ac companied by striking hyaline thickening in arteriolar walls even when the blood pressure and glomerular filtra tion rate are normal [1,2], It is not known whether this arteriolar change is important in the pathogenesis of the glomerular disease but similar changes are seen also in other lesions associated with the development of FGS, and particularly reflux nephropathy [3], Rats which de velop spontaneous FGS have been shown to have de creased plasma renin activity (PRA) and the PRA falls before histological lesions are evident [4], We have inves tigated patients with FGS who have normal renal func tion and blood pressure to see whether any failure of the renin-angiotensin system can be demonstrated. We chose to use measurement of the PRA and aldosterone as sup pression of the renin-angiotensin system (RAS) should be evident by a demonstration of low values during stimulation by upright body posture.…”

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No Evidence of Failure of the Renin-Angiotensin System in Focal Glomerulosclerosis in Man

Espiner

1986

Nephron

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Plasma Renin Activity Decrease Precedes Spontaneous Focal Glomerular Sclerosis in Aging Rats

Cited by 32 publications

References 13 publications

Differential effects of aging on fluid intake in response to hypovolemia, hypertonicity, and hormonal stimuli in Munich Wistar rats

Differential effects of aging on fluid intake in response to hypovolemia, hypertonicity, and hormonal stimuli in Munich Wistar rats

Glomerular Hyperfiltration, High Renin, and Low- Extracellular Volume in High Blood Pressure

No Evidence of Failure of the Renin-Angiotensin System in Focal Glomerulosclerosis in Man

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