Compartmentalization of angiotensin II generation in the dog heart. Evidence for independent mechanisms in intravascular and interstitial spaces
| Autor: | Suzanne Oparil, Louis J. Dell'Italia, Chih Chang Wei, Gilbert R. Hageman, Ronald Palmer, Qing C. Meng, Joan Durand, Gerald H. Hankes, Eduardo Balcells |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
medicine.medical_specialty
Microdialysis Captopril Angiotensin-Converting Enzyme Inhibitors Blood Pressure Peptidyl-Dipeptidase A Renin-Angiotensin System Dogs Interstitial space Heart Rate Interstitial fluid Internal medicine Renin–angiotensin system medicine Animals Chromatography High Pressure Liquid biology Chemistry Angiotensin II Myocardium General Medicine Coronary Vessels Perfusion Endocrinology Enzyme inhibitor cardiovascular system biology.protein Angiotensin I Extracellular Space Oligopeptides hormones hormone substitutes and hormone antagonists Research Article medicine.drug |
| Zdroj: | Journal of Clinical Investigation. 100:253-258 |
| ISSN: | 0021-9738 |
| Popis: | Angiotensin-converting enzyme inhibitors have beneficial effects that are presumably mediated by decreased angiotensin II (ANG II) production. In this study, we measure for the first time ANG I and ANG II levels in the interstitial fluid (ISF) space of the heart. ISF and aortic plasma ANG I and II levels were obtained at baseline, during intravenous infusion of ANG I (5 microM, 0.1 ml/min, 60 min), and during ANG I + the angiotensin-converting enzyme inhibitor captopril (cap) (2.5 mM, 0.1 ml/min, 60 min) in six anesthetized open-chested dogs. ISF samples were obtained using microdialysis probes inserted into the left ventricular myocardium (3-4 probes/dog). ANG I increased mean arterial pressure from 102+/-3 (SEM) to 124+/-3 mmHg (P < 0.01); addition of cap decreased MAP to 95+/-3 mmHg (P < 0.01). ANG I infusion increased aortic plasma ANG I and ANG II (pg/ml) (ANG I = 101+/-129 to 370+/-158 pg/ml, P < 0.01; and ANG II = 22+/-40 to 466+/-49, P < 0.01); addition of cap further increased ANG I (1,790+/-158, P < 0.01) and decreased ANG II (33+/-49, P < 0.01). ISF ANG I and ANG II levels (pg/ml) were > 100-fold higher than plasma levels, and did not change from baseline (8,122+/-528 and 6,333+/-677), during ANG I (8,269+/-502 and 6, 139+/-695) or ANG I + cap (8,753+/-502 and 5,884+/-695). The finding of very high ANG I and ANG II levels in the ISF vs. intravascular space that are not affected by IV ANG I or cap suggests that ANG II production and/or degradation in the heart is compartmentalized and mediated by different enzymatic mechanisms in the interstitial and intravascular spaces. |
| Databáze: | OpenAIRE |
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