Is Basal Microvascular Permeability Determined by PKA Activity?

Abstract

Sex-specific differences have been shown to exist in cardiovascular health and disease. Little is known, however, about the role of sex in the regulation of microvascular exchange, particularly microvessel permeability. Previously we have reported that basal permeability (Ps) to albumin of venules isolated from abdominal skeletal muscles was about 2-fold higher in adult male (AM) than adult female (AF), juvenile male (JM), or juvenile female (JF) rats. Further Ps did not differ among AF, JM and JF. It has been demonstrated in frog and rat mesentery that protein kinase A (PKA) played a dominant role in the maintenance of basal microvessel permeability. In this model, the PKA activity was inversely related to Ps. Accordingly, we hypothesized that the high Ps in the AM is the result of lower PKA activity than the other 3 groups and that PKA activity in these 3 groups would not differ. To test this hypothesis, we used primary cultured endothelial cells (EC) derived from the corresponding abdominal skeletal muscles of AM, AF, JM, and JF rats. We quantified the amount of active and inactive PKA in these 4 groups of EC under the resting conditions using immunoblot assay. We found that expression of inactive PKA C-α did not differ among 4 groups of EC (n=4). Of particular interest, PKA activity was not detectable in AF (n=4/4) or AM (n=3/4). In contract, the PKA activity, normalized to JF was 0.19 (n=1/4) and 0.46±0.12 (n=4) for AM and JM, respectively. These findings contrast with the hypothesis of PKA activity being exclusive determinant of basal Ps. The PKA activity data, therefore predict that Ps of AM=AF>>JM >JF in contrast to the observed relationship of AM>AF=JM=JF. Supported by NIH RO1HL078816, HL075186, 1CO6RR017353 and NASA NNJ05HF37G