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PubMedDate not supplied

Methods of suppression of myonephropathic metabolic syndrome.

Acute arterial occlusion of the extremities may result in severe and complex metabolic derangements. In order to investigate therapeutic means of controlling such metabolic derangements, 19 adult mongrel dogs weighing between 7 and 15 kg underwent acute arterial occlusion by cross-clamping the infrarenal aorta. Clamping was released after 48 hours. The experimental animals were divided into three groups: an untreated group, a THAM group, and a perfusion group. Biochemical and electrolyte analyses were measured before and 1 hour after occlusion, and 1, 3, 12, 24, and 48 hours after the release of occlusion. The SGOT, creatinine, CPK, and aldolase levels rose after release of the occlusion and were significantly higher in the untreated group than in the THAM and perfusion groups. Among these enzymatic changes, the CPK level showed the largest increase. The serum potassium levels remained almost at preocclusion levels after release of the occlusion. It was concluded that the intravenous administration of THAM and peripheral washing were effective against untoward metabolic changes occurring in the ischemic extremities.

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PubMedDate not supplied

Vasopressin release, water channels, and vasopressin antagonism in cardiac failure, cirrhosis, and pregnancy.

Vasopressin (AVP) is released in response to both osmotic and nonosmotic stimuli. Nonosmotic-stimulated AVP release occurs in cardiac failure, cirrhosis, and pregnancy in response to alterations in arterial circulatory integrity. Cardiac failure in rats is associated with increased plasma AVP and hypothalamic AVP mRNA, and in humans, it is associated with cardiac failure. Plasma AVP concentrations are elevated when measured with a sensitive radioimmunoassay. Urinary concentrations of AVP-responsive aquaporin-2 water channels are also elevated in cardiac failure. V2 receptor antagonists correct the impaired solute-free water excretion seen in rats with low-output cardiac failure and reverse the upregulation of renal aquaporin-2 water channels. Orally active non-peptide-selective V2 receptor antagonists administered to patients with congestive cardiac failure decrease urinary concentrations of aquaporin-2, increase solute-free water clearance, and correct the hyponatremia. Cirrhosis of the liver results in splanchnic arterial vasodilation and increased vascular capacity, most likely secondary to increased nitric oxide production. This relative underfilling of the arterial circulation stimulates nonosmotic AVP release with resultant water retention. Aquaporin-2 gene expression is upregulated in the kidneys of rats with cirrhosis of the liver. AVP-2 receptor antagonists administered to animals with cirrhosis reverse the water retention. Human studies using orally active, non-peptide-selective V2 receptor antagonists in patients with cirrhosis are currently underway. Pregnancy is another state of nitric oxide-mediated arterial vasodilation that is associated with plasma AVP concentrations that are relatively high for the degree of hypoosmolality. Upregulation of the water channel aquaporin-2 in the renal papillae of pregnant rats has also been demonstrated, and this effect is reversed by administration of a V2 receptor antagonist.

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