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Vascular remodeling in systemic hypertension
P Gohlke1, V Lamberty, I Kuwer
1Department of Pharmacology, University of Heidelberg, Germany.
Insights
Angiotensin-converting enzyme (ACE) inhibitors improve vascular function in hypertensive rats, even at low doses. These improvements occur independently of blood pressure control and structural vascular changes.
Area of Science:
- Cardiovascular Pharmacology
- Vascular Biology
- Hypertension Research
Background:
- Hypertension treatment requires more than blood pressure control.
- Vascular remodeling (hypertrophy/hyperplasia) is a key issue in hypertension.
- Antihypertensive treatments aim for structural and functional vascular improvements.
Purpose of the Study:
- To investigate the effects of ACE inhibitors on vascular remodeling and function.
- To assess if ACE inhibitors improve vascular function independently of blood pressure reduction.
- To evaluate both antihypertensive and sub-antihypertensive doses in a prevention study.
Main Methods:
- Spontaneously hypertensive rats were treated with ACE inhibitors (zabicipril, perindopril, ramipril).
- Treatment started before hypertension onset (prevention study).
- Vascular morphology (media:lumen ratio) and function (vasoconstriction/vasodilation) were analyzed.
Main Results:
- Antihypertensive doses of ACE inhibitors induced mesenteric vessel remodeling.
- Both high and low doses improved aortic vascular function.
- ACE inhibition attenuated vasoconstrictor responses and enhanced vasodilator responses.
- Aortic cyclic guanosine monophosphate (cGMP) content increased, indicating improved vasodilation.
Conclusions:
- ACE inhibitors improve vascular function independently of structural changes.
- Low doses of ACE inhibitors can enhance vascular function without significant antihypertensive effects.
- ACE inhibitors offer benefits beyond blood pressure lowering in hypertension management.
Abstract:
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.