ramipril and zabicipril

The length density (Lv) of capillaries is known to be increased in the hearts of spontaneously hypertensive rats (SHR) after high-dosed but also after low-dosed subantihypertensive treatment with the ACE-inhibitor Ramipril administered in utero and post partum. Under the same conditions in the present study only high-dose Zabicipril caused an increase of capillary Lv. Under preventive ACE-inhibition in both high-dose groups Lv of myocardial arteries was significantly higher. In the low-dose groups Lv was not significantly increased. The increased arterial Lv in the high-dose-group may result from the avoidance of angiotensin II-induced overabundant growth of myocardial muscle-mass. Changes in collagen could not be found in any of the experimental groups.

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Bridged Bicyclo Compounds, Heterocyclic; Capillaries; Coronary Vessels; Dose-Response Relationship, Drug; Hypertension; Myocardium; Neovascularization, Pathologic; Organ Size; Ramipril; Random Allocation; Rats; Rats, Inbred SHR; Vasoconstrictor Agents

It is now well accepted that treatment of hypertension must extend beyond the mere control of blood pressure. Among the objectives "beyond blood pressure control" is the remodeling of resistance and compliance vessels that have usually undergone a process of hypertrophy and/or hyperplasia. Salutary vascular remodeling by antihypertensive treatment not only implies structural changes of the vascular wall, but also functional improvements, including diminished contractile responses to endogenous vasoconstrictors and enhanced relaxation to endogenous vasodilators. We have treated spontaneously hypertensive rats with the angiotensin-converting enzyme (ACE) inhibitors zabicipril, perindopril, and ramipril at antihypertensive and sub-antihypertensive doses and have analyzed vascular morphology and function. Chronic oral treatment was begun before hypertension developed (prevention study). Remodeling of mesenteric vessels with, inter alia, a reduction of the media:lumen ratio was achieved by antihypertensive doses of the drugs. Further, vascular function was improved not only after high-dose, but also after low-dose ACE inhibitor treatment, as tested in the aortic vessels: an inhibition of vascular ACE was associated with attenuated vasoconstrictor responses to norepinephrine and enhanced dilator responses to acetylcholine. In addition, low and high doses significantly increased aortic cyclic guanosine monophosphate (cGMP) content, suggesting an improved vasodilator capacity. Our data demonstrate that improvements of vascular function can be achieved by ACE inhibitors, independently of structural changes and of the antihypertensive action exerted by these drugs.

Topics: Acetylcholine; Angiotensin-Converting Enzyme Inhibitors; Animals; Bridged Bicyclo Compounds; Bridged Bicyclo Compounds, Heterocyclic; Cyclic GMP; Hypertension; Indoles; Muscle, Smooth, Vascular; Perindopril; Ramipril; Rats; Rats, Inbred SHR; Vasoconstriction; Vasodilation