CAPILLARY HYDRAULIC CONDUCTIVITY IS ELEVATED BY CGMP-DEPENDENT VASODILATORS

Microvascular functions have been shown to be sensitive to agents associated with changes in cyclic nucleotide levels. The central hypothesis of the current study was that one measure of capillary exchange capacity, hydraulic conductivity (L(p)), would be elevated by agents shown to elevate cellular levels of cGMP. To evaluate the hypothesis, frog mesenteric capillary L, was measured during luminal exposure to 1) atrial natriuretic peptide (ANP), 2) the truncated atriopeptins ANP-I and ANP-III, 3) the nitrovasodilator sodium nitroprusside (SNP), 4) the cGMP phosphodiesterase inhibitor M&B 22948, and 5) methylene blue dye, both alone and in combination with ANP or SNP. ANP (100 nM) elevated L(p) by 2.3 +/- 0.2-fold from control levels (n = 15); 10 nM ANP induced a 2.1 +/- 0.3-fold change (n = 8), while 10 nM ANP-III elicited a 1.7 +/- 0.4-fold change (n = 8). In contrast, L(p) did not change from basal levels during 10 nM ANP-I infusion (L(p)ANP-I/L(p) control = 1.2 +/- 0.2; n = 14). SNP (1-mu-M) induced a reversible, 2.6 +/- 0.5-fold increase in L(P) (n = 30) that was inhibitable by methylene blue dye (L(p)SNP+MetB/L(p) control = 1.1 +/- 0.1; n = 8). Methylene blue did not mask the response to 100 nM ANP (L(p) ANP+MetB/L(p) control = 2.1 +/- 0.5; n = 7). M&B 22948 (30-mu-M) increased L(p) by 2.8 +/- 0.6-fold (n = 9). These data constitute strong inference that agents demonstrated to elevate cGMP also mediate an increase in capillary L(p) in in situ, perfused exchange vessels.