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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 (Lp), would be elevated by agents shown to elevate cellular levels of cGMP. To evaluate the hypothesis, frog mesenteric capillary Lp 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 Lp 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, Lp did not change from basal levels during 10 nM ANP-I infusion (LpANP-1/Lpcontrol=1.2±0.2; n=14). SNP (1 μM) induced a reversible, 2.6±0.5-fold increase in Lp (n=30) that was inhibitable by methylene blue dye (LpSNP+MetB/Lpcntrol=1.1±0.1; n=8). Methylene blue did not mask the response to 100 nM ANP (LpANP+MetB/Lpcontrol=2.1±0.5; n=7). M&B 22948 (30 μM) increased Lp 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 Lp in in situ, perfused exchange vessels.