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Angiotensin-converting enzyme inhibitors, inhibition of brain and peripheral angiotensin-converting enzymes, and left ventricular dysfunction in rats after myocardial infarction.
J Cardiovasc Pharmacol. 2008 Jun; 51(6):565-72.JC

Abstract

BACKGROUND

The brain renin-angiotensin system contributes significantly to progressive left ventricular (LV) dysfunction in rats after myocardial infarction (MI). The present study evaluated the effects of central versus peripheral plus central angiotensin-converting enzyme (ACE) blockade on sympathetic activity, and LV anatomy and function after MI.

METHODS

Wistar rats were treated for 4 weeks after MI with the lipophilic ACE inhibitor trandolapril at 5 mg/kg/day or the hydrophilic blocker lisinopril at 50 mg/kg/day by once daily subcutaneous injection, or with a central infusion of lisinopril at 0.1 mg/kg/day.

RESULTS

At 24 hours after the last dose, subcutaneous trandolapril caused 70% to 80% ACE inhibition in both brain and kidneys; lisinopril caused 10% to 20% less. Central infusion of lisinopril caused 70% inhibition of brain ACE and minimal (6%) inhibition in the kidneys. All three treatments similarly improved sympathetic reactivity and arterial baroreflex function. All three treatments lowered cardiac Ang I and II, and similarly attenuated the increases in LV end diastolic pressure, circumference, and fibrosis. Both subcutaneous treatments further decreased LV peak systolic pressure and dP/dt max, whereas icv lisinopril caused no change.

CONCLUSION

Despite marked differences in the extent of peripheral blockade, all three treatments similarly affected sympathetic activity and decreased cardiac Ang II, preload and remodeling after MI. One may speculate that central and peripheral ACE-mediated mechanisms are sequential and therefore only minor additional effects of peripheral ACE blockade are noted.

Authors+Show Affiliations

Hypertension Unit, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18496146

Citation

Ahmad, Monir, et al. "Angiotensin-converting Enzyme Inhibitors, Inhibition of Brain and Peripheral Angiotensin-converting Enzymes, and Left Ventricular Dysfunction in Rats After Myocardial Infarction." Journal of Cardiovascular Pharmacology, vol. 51, no. 6, 2008, pp. 565-72.
Ahmad M, White R, Tan J, et al. Angiotensin-converting enzyme inhibitors, inhibition of brain and peripheral angiotensin-converting enzymes, and left ventricular dysfunction in rats after myocardial infarction. J Cardiovasc Pharmacol. 2008;51(6):565-72.
Ahmad, M., White, R., Tan, J., Huang, B. S., & Leenen, F. H. (2008). Angiotensin-converting enzyme inhibitors, inhibition of brain and peripheral angiotensin-converting enzymes, and left ventricular dysfunction in rats after myocardial infarction. Journal of Cardiovascular Pharmacology, 51(6), 565-72. https://doi.org/10.1097/FJC.0b013e318177090d
Ahmad M, et al. Angiotensin-converting Enzyme Inhibitors, Inhibition of Brain and Peripheral Angiotensin-converting Enzymes, and Left Ventricular Dysfunction in Rats After Myocardial Infarction. J Cardiovasc Pharmacol. 2008;51(6):565-72. PubMed PMID: 18496146.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Angiotensin-converting enzyme inhibitors, inhibition of brain and peripheral angiotensin-converting enzymes, and left ventricular dysfunction in rats after myocardial infarction. AU - Ahmad,Monir, AU - White,Roselyn, AU - Tan,Junhui, AU - Huang,Bing S, AU - Leenen,Frans H H, PY - 2008/5/23/pubmed PY - 2008/10/9/medline PY - 2008/5/23/entrez SP - 565 EP - 72 JF - Journal of cardiovascular pharmacology JO - J Cardiovasc Pharmacol VL - 51 IS - 6 N2 - BACKGROUND: The brain renin-angiotensin system contributes significantly to progressive left ventricular (LV) dysfunction in rats after myocardial infarction (MI). The present study evaluated the effects of central versus peripheral plus central angiotensin-converting enzyme (ACE) blockade on sympathetic activity, and LV anatomy and function after MI. METHODS: Wistar rats were treated for 4 weeks after MI with the lipophilic ACE inhibitor trandolapril at 5 mg/kg/day or the hydrophilic blocker lisinopril at 50 mg/kg/day by once daily subcutaneous injection, or with a central infusion of lisinopril at 0.1 mg/kg/day. RESULTS: At 24 hours after the last dose, subcutaneous trandolapril caused 70% to 80% ACE inhibition in both brain and kidneys; lisinopril caused 10% to 20% less. Central infusion of lisinopril caused 70% inhibition of brain ACE and minimal (6%) inhibition in the kidneys. All three treatments similarly improved sympathetic reactivity and arterial baroreflex function. All three treatments lowered cardiac Ang I and II, and similarly attenuated the increases in LV end diastolic pressure, circumference, and fibrosis. Both subcutaneous treatments further decreased LV peak systolic pressure and dP/dt max, whereas icv lisinopril caused no change. CONCLUSION: Despite marked differences in the extent of peripheral blockade, all three treatments similarly affected sympathetic activity and decreased cardiac Ang II, preload and remodeling after MI. One may speculate that central and peripheral ACE-mediated mechanisms are sequential and therefore only minor additional effects of peripheral ACE blockade are noted. SN - 1533-4023 UR - https://www.unboundmedicine.com/medline/citation/18496146/Angiotensin_converting_enzyme_inhibitors_inhibition_of_brain_and_peripheral_angiotensin_converting_enzymes_and_left_ventricular_dysfunction_in_rats_after_myocardial_infarction_ L2 - https://doi.org/10.1097/FJC.0b013e318177090d DB - PRIME DP - Unbound Medicine ER -