Danser A H, van Kats J P, Admiraal P J, Derkx F H, Lamers J M, Verdouw P D, Saxena P R, Schalekamp M A
Department of Pharmacology, Cardiovasculair Onderzoeksinstituut Erasmus Universiteit Rotterdam, The Netherlands.
Hypertension. 1994 Jul;24(1):37-48. doi: 10.1161/01.hyp.24.1.37.
The existence of a cardiac renin-angiotensin system, independent of the circulating renin-angiotensin system, is still controversial. We compared the tissue levels of renin-angiotensin system components in the heart with the levels in blood plasma in healthy pigs and 30 hours after nephrectomy. Angiotensin I (Ang I)-generating activity of cardiac tissue was identified as renin by its inhibition with a specific active site-directed renin inhibitor. We took precautions to prevent the ex vivo generation and breakdown of cardiac angiotensins and made appropriate corrections for any losses of intact Ang I and II during extraction and assay. Tissue levels of renin (n = 11) and Ang I (n = 7) and II (n = 7) in the left and right atria were higher than in the corresponding ventricles (P < .05). Cardiac renin and Ang I levels (expressed per gram wet weight) were similar to the plasma levels, and Ang II in cardiac tissue was higher than in plasma (P < .05). The presence of these renin-angiotensin system components in cardiac tissue therefore cannot be accounted for by trapped plasma or simple diffusion from plasma into the interstitial fluid. Angiotensinogen levels (n = 11) in cardiac tissue were 10% to 25% of the levels in plasma, which is compatible with its diffusion from plasma into the interstitium. Like angiotensin-converting enzyme, renin was enriched in a purified cardiac membrane fraction prepared from left ventricular tissue, as compared with crude homogenate, and 12 +/- 3% (mean +/- SD, n = 6) of renin in crude homogenate was found in the cardiac membrane fraction and could be solubilized with 1% Triton X-100. Tissue levels of renin and Ang I and II in the atria and ventricles were directly correlated with plasma levels (P < .05), and in both tissue and plasma the levels were undetectably low after nephrectomy. We conclude that most if not all renin in cardiac tissue originates from the kidney. Results support the contentions that in the healthy heart, angiotensin production depends on plasma-derived renin and that plasma-derived angiotensinogen in the interstitial fluid is a potential source of cardiac angiotensins. Binding of renin to cardiac membranes may be part of a mechanism by which renin is taken up from plasma.
独立于循环肾素 - 血管紧张素系统之外的心脏肾素 - 血管紧张素系统的存在仍存在争议。我们比较了健康猪以及肾切除术后30小时心脏中肾素 - 血管紧张素系统各成分的组织水平与血浆中的水平。通过用特异性活性位点导向的肾素抑制剂抑制，心脏组织中生成血管紧张素I（Ang I）的活性被鉴定为肾素。我们采取了预防措施以防止心脏血管紧张素在体外生成和分解，并对提取和测定过程中完整的Ang I和II的任何损失进行了适当校正。左、右心房中肾素（n = 11）、Ang I（n = 7）和II（n = 7）的组织水平高于相应心室（P <.05）。心脏肾素和Ang I水平（以每克湿重表示）与血浆水平相似，心脏组织中的Ang II高于血浆（P <.05）。因此，心脏组织中这些肾素 - 血管紧张素系统成分的存在不能用滞留的血浆或从血浆简单扩散到组织间隙来解释。心脏组织中血管紧张素原水平（n = 11）为血浆水平的10%至25%，这与其从血浆扩散到组织间隙相符。与粗匀浆相比，肾素在从左心室组织制备的纯化心脏膜组分中富集，粗匀浆中12±3%（平均值±标准差，n = 6）的肾素存在于心脏膜组分中，并且可以用1% Triton X - 100溶解。心房和心室中肾素、Ang I和II的组织水平与血浆水平直接相关（P <.05），肾切除术后组织和血浆中的水平均低至检测不到。我们得出结论，心脏组织中大多数（如果不是全部）肾素起源于肾脏。结果支持以下观点：在健康心脏中，血管紧张素的产生依赖于血浆来源的肾素，并且组织间隙中血浆来源的血管紧张素原是心脏血管紧张素的潜在来源。肾素与心脏膜的结合可能是肾素从血浆中摄取的一种机制的一部分。
