Sexual dimorphism in the aging kidney: Effects on injury and nitric oxide system.

Background: Male gender confers enhanced susceptibility to development of age-dependent kidney damage. In other models of progressive renal disease, development of injury is linked to declines in renal nitric oxide synthase (NOS) capacity.

Methods: We investigated the in vitro characteristics of the renal NOS system in young (3 to 5 months), middle-aged (11 to 13 months) and old (18 to 22 months) male and female Sprague-Dawley rats.

Osteoporosis in the Cohen diabetic rat: correlation between histomorphometric changes in bone and microangiopathy.

Osteoporosis is well documented in type I diabetes, but its occurrence is controversial in type II diabetes. Microangiopathy is a major complication of type I and type II diabetes. We studied bone and microvascular changes in the Cohen diabetic rat, a unique nonobese model of noninsulin-dependent diabetes mellitus.

The 'intestinal-renal' arginine biosynthetic axis in the aging rat.

It has been suggested that L-arginine availability declines with advanced age, which could contribute to the endothelial dysfunction and decreased nitric oxide (NO) production that are features of aging. L-Arginine is made in the kidney and since the aging kidney develops progressive injury there may be decreased synthesis limiting availability. In this study we investigated the impact of aging on the regulation, at the gene level, of the various enzymes that synthesize L-arginine in the kidney (argininosuccinate synthetase and argininosuccinate lyase) and citrulline, the precursor of L-arginine made in the small intestine (phosphate-dependent glutaminase, carbamyl phosphate synthetase-1 and ornithine transcarbamylase).

Acute neutral endopeptidase inhibition is natriuretic in old rats.

Neutral endopeptidase 24.11 (NEP) inhibitors prevent breakdown of atrial natriuretic peptide (ANP), and may be useful therapeutically, in sodium overload states as often occurs in the aged. However, age-dependent changes in ANP/NEP may limit the activity of these agents in the elderly.

The role of endothelin in the age dependent increase in renal vascular resistance in the rat kidney.

Endothelin (ET) is a powerful vasopressor agent that is activated in a number of pathophysiologic states where renal perfusion is reduced. Since renal vasoconstriction occurs as part of renal aging, we investigated the possibility that ET may be activated in the old kidney. These experiments involved acutely blocking endogenous ET with Bosentan (a non-peptide mixed antagonist to both ET receptor types ETA and ETB), in Sprague-Dawley male rats of various ages: young (4 5 months), middle-aged (12-13 months) and old (19-20 months).