Meyer D J, Huxley V H
Department of Physiology, University of Missouri School of Medicine, Columbia 65212.
Circ Res. 1992 Feb;70(2):382-91. doi: 10.1161/01.res.70.2.382.
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 (Lp ANP-I/Lp control = 1.2 +/- 0.2; n = 14). SNP (1 microM) induced a reversible, 2.6 +/- 0.5-fold increase in Lp (n = 30) that was inhibitable by methylene blue dye (Lp SNP + MetB/Lp control = 1.1 +/- 0.1; n = 8). Methylene blue did not mask the response to 100 nM ANP (Lp ANP + MetB/Lp control = 2.1 +/- 0.5; n = 7). M&B 22948 (30 microM) 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.
微血管功能已被证明对与环核苷酸水平变化相关的药物敏感。本研究的核心假设是,一种衡量毛细血管交换能力的指标——水力传导率(Lp),会被证明能提高细胞内cGMP水平的药物所升高。为了评估这一假设,在向蛙肠系膜毛细血管腔内暴露以下物质期间测量Lp:1)心房利钠肽(ANP),2)截短的心房肽ANP-I和ANP-III,3)硝基血管扩张剂硝普钠(SNP),4)cGMP磷酸二酯酶抑制剂M&B 22948,以及5)亚甲蓝染料,单独使用以及与ANP或SNP联合使用。ANP(100 nM)使Lp较对照水平升高2.3±0.2倍(n = 15);10 nM ANP引起2.1±0.3倍的变化(n = 8),而10 nM ANP-III引起1.7±0.4倍的变化(n = 8)。相比之下,在输注10 nM ANP-I期间,Lp与基础水平相比没有变化(Lp ANP-I/Lp对照 = 1.2±0.2;n = 14)。SNP(1 μM)使Lp可逆性升高2.6±0.5倍(n = 30),该升高可被亚甲蓝染料抑制(Lp SNP + MetB/Lp对照 = 1.1±0.1;n = 8)。亚甲蓝并未掩盖对100 nM ANP的反应(Lp ANP + MetB/Lp对照 = 2.1±0.5;n = 7)。M&B 22948(30 μM)使Lp升高2.8±0.6倍(n = 9)。这些数据有力地推断出,已证明能升高cGMP的药物在原位灌注的交换血管中也介导毛细血管Lp的增加。