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Cardiac and aortic effects of angiotensin converting enzyme inhibitors
1Alton Ochsner Medical Foundation, New Orleans, La 70121.
Insights
Different angiotensin converting enzyme inhibitors showed similar hemodynamic effects but variable impacts on cardiac structure and function in rats. This dissociation suggests underlying pharmacokinetic or pharmacodynamic differences.
Area of Science:
- Cardiovascular Pharmacology
- Renal System Physiology
Background:
- Angiotensin converting enzyme inhibitors (ACE inhibitors) are widely used antihypertensives.
- Their effects on cardiovascular structure and function, particularly in hypertensive models, warrant further investigation.
Purpose of the Study:
- To compare the effects of six ACE inhibitors on cardiovascular parameters in Wistar-Kyoto and spontaneously hypertensive rats.
- To investigate potential dissociation between hemodynamic effects, cardiac structure, and cardiac function.
Main Methods:
- Male Wistar-Kyoto and spontaneously hypertensive rats received daily oral administration of six ACE inhibitors or control for 3 weeks.
- Evaluated cardiovascular structure, systemic hemodynamics, left ventricular end-diastolic pressure, left ventricular pumping ability, and aortic distensibility.
Main Results:
- ACE inhibitors generally produced similar hemodynamic effects.
- Cardiac mass reduction varied among agents, occurring in both hypertrophied and non-hypertrophied chambers.
- Changes in left ventricular pumping ability were not consistently linked to changes in cardiac mass or aortic distensibility.
Conclusions:
- Hemodynamic alterations induced by ACE inhibitors were associated with inconsistent changes in cardiovascular structure and function.
- Dissociated responses may stem from pharmacokinetic/pharmacodynamic variations or differential effects on local renin-angiotensin systems.
Abstract:
The effects of six angiotensin converting enzyme inhibitors (captopril, CGS-16617, cilazapril, enalapril, utibapril, and quinapril) on cardiovascular structure, systemic hemodynamics, left ventricular end-diastolic pressure, left ventricular pumping ability, and aortic distensibility were assessed in male normotensive Wistar-Kyoto and spontaneously hypertensive rats 16-19 weeks of age. Rats (10 in each group) were treated for 3 weeks with drugs or control diluents administered daily by gavage. The agents, in general, had similar hemodynamic effects, although these effects on cardiac mass were variable; some agents reduced left ventricular mass and some produced no change. These effects occurred in hypertrophied as well as nonhypertrophied chambers. Furthermore, changes in left ventricular pumping ability were not necessarily related to the ability of these agents to change left ventricular mass; this dissociation in performance was neither related to change in structure nor to changes in aortic distensibility. Thus, even within a same class of antihypertensive agents (i.e., angiotensin converting enzyme inhibitors), similarly induced hemodynamic alterations were associated with inconsistent changes in left ventricular pumping ability or aortic distensibility regardless of whether the structure was hypertrophied before therapy. These dissociated responses in cardiovascular structure and function may be related to pharmacodynamic or pharmacokinetic differences; alternatively, they also may be related to these differences in action on local myocytic renin-angiotensin systems or in intramyocytic biological responses.