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Interactions between coronary occlusion and the renin-angiotensin system in the dog

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Summary

Studies were carried out in 39 barbiturate-anesthetized dogs to determine whether the renin-angiotensin system is important in control of hemodynamics and coronary flow during myocardial ischemia. Plasma renin activity (PRA) was 2.2±0.4 ng·ml−1·hr−1 immediately before coronary artery occlusion (CAO) and increased to 3.8±0.5 (p<.005) 15 minutes after CAO. In nephrectomized dogs, PRA was 0.76±0.14 ng·ml−1·hr−1 two hours after nephrectomy and remained unchanged after CAO. In contrast, hemodynamic changes following CAO were similar between nephrectomized and intact dogs: mean arterial pressure fell from 126±4 pre CAO to 116±4 mm Hg post CAO (p<0.005) in nephrectomized dogs and from 130±11 to 120±11 mm Hg (p<0.005) in intact dogs. Left atrial pressure rose from 5.4±0.9 pre CAO to 7.7±0.9 mm Hg (p<0.005) post CAO in nephrectomized dogs and 6.3±1.3 to 9.0±1.8 mm Hg (p<0.005) in intact dogs. Heart rate remained unchanged in both groups. In sham-operated dogs without CAO, neither the angiotensin II blocker Saralasin nor the converting enzyme inhibitor Captopril had significant effects on systemic (SVR) and coronary (CVR) vascular resistances. In contrast, in dogs with CAO, these drugs reduced CVR from 1.28±0.13 mm Hg·ml−1·min·100 g heart weight (resistance units=RU) to 0.85±0.08 RU (p<0.05) (Saralasin) 15 minutes after treatment and from 1.17±0.09 to 0.88±0.08 RU (p<0.025), (Captopril) respectively. However, only Captopril reduced SVR, from 10.7±1.13 to 8.2±0.8 RU (p<0.025). Both Captopril and Saralasin induced a significant increase in collateral blood flow. Nephrectomy, two hours prior to CAO, significantly reduced the effect of Captopril on CVR and collateral blood flow while the effect on SVR persisted. Thus the reduction in CVR appears to be an effect of inhibition of the renin-angiotensin system; this system participates in control of CVR during CAO and may limit coronary collateral blood flow.

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Author notes

  1. G. Ertl

    Present address: Med. Klinik d. Univ. Würzburg, Josef-Schneider-Straße 2, 8700, Würzburg

Authors and Affiliations

  1. Harvard Medical School, Boston, Massachusetts

    G. Ertl, R. W. Alexander & R. A. Kloner

  2. Brigham and Women's Hospital, Boston, Massachusetts

    G. Ertl, R. W. Alexander & R. A. Kloner

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  2. R. W. Alexander
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Supported by Grant er 100/1 of the DFG and by Grants HL-23140 and HL-26215 from the National Heart, Lung, and Blood Institute, USA.

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Ertl, G., Alexander, R.W. & Kloner, R.A. Interactions between coronary occlusion and the renin-angiotensin system in the dog. Basic Res Cardiol 78, 518–533 (1983). https://doi.org/10.1007/BF01906463

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