trandolapril and Hypoxia

Cardiac hypertrophy due to a chronic mechanical overload puts into play a biologic cascade, including a trigger (the mechanical stretch), a transmitter (very likely to be the phosphoinositol pathway), and the final target (which is the DNA). The permanent changes in genetic expression resulting from the activation of this cascade allows the heart to produce normal active tension at a lower cost in terms of energy expenditure. The process is reversible, providing the treatment reduces the real load on the heart--i.e., not only the peripheral resistances but also the aortic impedance--during a period of time that has to be several times the half-life of cardiac proteins, and also that the treatment has an effect on the detrimental consequences of cardiac hypertrophy, namely, the systolic and diastolic dysfunction and the incidence of arrhythmias. In this report semisenescent spontaneously hypertensive rats were treated for 3 months with the converting enzyme inhibitor trandolapril. The treatment had a rather modest effect on blood pressure but resulted in a pronounced reduction in cardiac hypertrophy and in cardiac fibrosis, an improved coronary reserve, and attenuated both the effects of anoxia on the left ventricular diastolic compliance and the incidence of ventricular arrhythmias.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Arrhythmias, Cardiac; Humans; Hypertrophy, Left Ventricular; Hypoxia; Indoles; Male; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Ventricular Function, Left

1. Dogs were exposed to hypoxemia followed by a coronary angiogram at three different times: under control conditions, after ischemia-reperfusion injury, then 30 min later. 2. In the study group, the dogs were treated with trandolapril (0.05 mg/kg) and verapamil (0.1 mg/ kg) just prior to the final hypoxic challenge. 3. Under control conditions, the left anterior descending coronary artery (LAD) dilated in response to hypoxia. Following ischemia-reperfusion injury, however, it constricted significantly in response. 4. In the control group, repeat hypoxia 30 min later resulted in vasoconstriction of the LAD which was comparable to the preceding response. 5. However, in the study group, treatment with trandolapril plus verapamil inhibited the vasoconstriction in response to repeat hypoxia.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Calcium Channel Blockers; Coronary Vasospasm; Dogs; Drug Therapy, Combination; Female; Hypoxia; Indoles; Male; Myocardial Reperfusion Injury; Verapamil

The effects of trandolapril, a converting enzyme inhibitor (CEI), on left ventricular (LV) diastolic stiffness and coronary vascular resistance (CVR), were studied with an isolated heart preparation in 15-month-old spontaneously hypertensive rats (SHR). The hypertensive animals were treated for 3 months with trandolapril (0.3 mg/kg/day) (SHRT), and compared with untreated age-matched Wistar-Kyoto rats (WKY) and SHR. Trandolapril treatment resulted in 15% diminution in blood pressure (BP). In contrast, it completely normalized left ventricular (LV) weight. Untreated SHR, as compared with WKY, had a dilated LV and increased diastolic tissue stiffness. Trandolapril had no effect on either chamber or tissue stiffness. Five-minute anoxia resulted in the same dramatic increase in chamber stiffness in every experimental group. During anoxia, as during normoxia, tissue stiffness was still greater in SHR than in WKY. A major effect of CEI was to normalize the tissue stiffness of SHR under anoxia. Coronary vascular resistance (CVR) was increased in SHR as compared with WKY. Trandolapril improves CVR and significantly shifts the coronary pressure flow curve to the dilatory side. Both collagen concentration (approximately 2 mg/g) and the content in slow V3 myosin isoform, used as biologic markers of cardiac senescence, were the same in the three experimental groups, but higher than in young hearts. Trandolapril had no effect on these parameters. In semisenescent SHR, despite having rather slight effect on arterial pressure, trandolapril completely normalized LV weight. In addition, collagen content and its physiologic counterpart, tissue stiffness, were unaffected by 3-month treatment with trandolapril. Nevertheless, the anoxia-induced increase in LV tissue stiffness was improved by trandolapril in parallel with reduction in LV hypertrophy (LVH).

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Coronary Vessels; Disease Models, Animal; Heart Ventricles; Hypertension; Hypertrophy, Left Ventricular; Hypoxia; In Vitro Techniques; Indoles; Male; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Vascular Resistance