Alterations in autonomic adjustments to acute hypoxia in conscious rats with aging.

Abstract

The experimental objective was to determine whether sympathetic nervous system activity and cardiovascular adjustments to hypoxia are altered with advancing age. Norepinephrine (NE) synthesis was blocked with alpha-methyl-DL-p-tyrosine, and NE turnover rates were determined in the left ventricle of the heart, kidney, liver, and adrenal gland in groups of conscious unrestrained mature (12-mo-old) and senescent (24-mo-old) Fischer 344 rats in conditions of normoxia and acute hypocapnic hypoxia (10% O2-90% N2). Calculated NE turnover rates were similar in all four tissues sampled for both age groups in the normoxic condition. Thirty minutes of hypoxia produced elevations in NE turnover rates in the kidney, liver, and adrenal gland, but not in the heart, for both the mature and senescent groups. However, NE turnover rates were attenuated in the kidney (92 vs. 195%) and liver (119 vs. 190%) of senescent compared with mature rats. Hypoxia produced no change in mean arterial pressure from normoxic levels in the mature rats, whereas older rats had a progressive decline in mean arterial pressure (-24 +/- 3 mmHg from baseline) over the course of the hypoxic exposure. In contrast, heart rate responses were similar in the normoxic and hypoxic conditions for both age groups. These findings indicate that sympathetic nerve activity, as estimated from NE turnover rates, increases in a tissue-specific manner with moderate hypoxia, but this increase is markedly attenuated in the kidney and liver with advancing age. In addition, the ability to maintain MAP during a hypoxic challenge is impaired with aging, perhaps due, in part, to a reduced sympathetic vasoconstriction to selected internal organs.