Abstract-Cardiac hypertrophy is often associated with an increased sympathetic drive, and both in vitro and in vivo studies have demonstrated the development of cardiomyocyte hypertrophy in response to either ␣-or ␤-adrenergic stimulation. Because an association between the Na ϩ /H ϩ exchanger and cellular growth has been proposed, this study aimed to analyze the possible role of the antiporter in isoproterenol-induced cardiac hypertrophy. Isoproterenol alone (5 mg/kg IP once daily) or combined with a selective inhibitor of the Na ϩ /H ϩ exchanger activity (3 mg · kg) was given to male Wistar rats for 30 days. Sex-and age-matched rats that received 0.9% saline IP daily served as controls. Echocardiographic follow-up showed a 33% increase in left ventricular mass in the isoproterenol-treated group, whereas it did not increase in the isoproterenolϩBIIB723-treated group. Heart weight-to-body weight ratio at necropsy was 2.44Ϯ0.11 in controls and increased to 3.35Ϯ0.10 (PϽ0.05) with isoproterenol, an effect that was markedly attenuated by BIIB723 (2.82Ϯ0.07). Intense cardiomyocyte enlargement and severe subendocardial fibrosis were found in isoproterenol-treated rats, and both effects were attenuated by BIIB723. Myocardial Na ϩ /H ϩ exchanger activity and protein expression significantly increased in isoproterenol-treated rats compared with the control group (1.45Ϯ0.11 vs 0.91Ϯ0.05 arbitrary units, PϽ0.05). This effect was significantly reduced by BIIB723 (1.17Ϯ0.02, PϽ0.05). In conclusion, our results show that Na ϩ /H ϩ exchanger inhibition prevented the development of isoproterenolinduced hypertrophy and fibrosis, providing strong evidence in favor of a key role played by the antiporter in this model of cardiac hypertrophy. Key Words: hypertrophy, cardiac Ⅲ signal transduction Ⅲ antiporters Ⅲ fibrosis Ⅲ adrenergic receptor agonists I ncreased sympathetic activity is often implicated in the development of cardiac hypertrophy (CH). A correlation between cardiac mass and sympathetic activity was found in young hypertensive humans, 1 and long-term infusion of subpressor doses of norepinephrine leads to CH in dogs and rats. 2,3 This cardiotrophic effect of catecholamines involves both ␣-or ␤-adrenergic receptors. 4 It is well recognized that repeated or continuous injections of the ␤-adrenoceptor agonist isoproterenol (Iso) causes, within days, clear CH, 5 and therefore it represents a useful experimental model.Although several mechanisms have been imputed to underlie the cardiotrophic action of Iso, 5-7 the exact nature is still under debate. Because cumulative evidence supports a cause-effect link between the activity of the Na ϩ /H ϩ exchanger (NHE) and cardiac cell growth (Cingolani and Camilión de Hurtado 8 ), we sought to analyze the possible role of NHE activity in Iso-induced CH by taking advantage of the specific, orally active inhibitor against NHE isoform 1 (NHE-1). This study provides evidence indicating a key role for NHE-1 activity as a mechanism underlying the development of CH and fibrosis induced by I...

The effect of 22∶6ω3 acid provided by dietary fish oil on the development of germinal tissue of rat testes, fatty acid composition of lipids, and linoleic or α‐linolenic acid Δ6 desaturation capacity was investigated. Results were compared to those obtained in animals fed methyl palmitate and sunflower seed oil (linoleate). At 7 and 9 weeks of age, development of germinal tissue of animals fed fish oil was normal. The fatty acid composition showed a decrease in 22∶5ω6 acid content and an increase in 22∶6ω3 acid in triacylglycerol, phosphatidylcholine, and phosphatidylethanolamine. The fatty acid Δ6 desaturation capacity of testicules microsomes was increased. It is suggested that 22∶6ω3 acid may functionally replace 22∶5ω6 acid in germinal tissue.

Aging produces alterations in certain functions of the hypothalamo-pituitary axis that result in sexually dimorphic changes in the somatotrophs. Since quantitative morphological data on these age-associated alterations are scarce, we prompted to make a morphometric immunohistochemical assessment as well as undertake an ultrastructural study of the somatotrophic (GH) cell population in male and female rats of different ages. Young (3-month-old), old (20-month-old), and senescent (29-month-old) Sprague-Dawley rats of both sexes were sacrificed by rapid decapitation, their pituitaries immediately dissected out, and processed for both immunohistochemistry and electron microscopy. Analysis of different morphometric parameters revealed that surface density, volume density, and cell density significantly decreased in old and senescent rats as compared to young animals, with this reduction being clearly more marked in females. Both the GH-cell area and perimeter decreased in senescent male rats, while these parameters increased in senescent females. The ultrastructure of the GH cells from old and senescent animals of both sexes evinced changes suggestive of an immature state, with some somatotrophs having the appearance of cells undergoing an involutive process. We conclude that aging has a differential impact on the GH cells of male and female rats with respect to the immunohistochemical and ultrastructural features of that cell population.