Vascular remodeling in systemic hypertension.
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.
Department of Pharmacology, University of Heidelberg, Germany.
P
P
Gohlke
V
V
Lamberty
I
I
Kuwer
S
S
Bartenbach
A
A
Schnell
T
T
Unger
D000109:Acetylcholine / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D006152:Cyclic GMP / Q000032:analysis; D006973:Hypertension / Q000503:physiopathology* / Q000517:prevention & control; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D020913:Perindopril; D017257:Ramipril / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007211:Indoles; C065499:zabicipril; D006152:Cyclic GMP; D017257:Ramipril; D000109:Acetylcholine; D020913:Perindopril