Comparative effects of the angiotensin II receptor blocker, telmisartan, and the angiotensin-converting enzyme inhibitor, ramipril, on cerebrovascular structure in spontaneously hypertensive rats.
OBJECTIVE
Antihypertensive treatment with angiotensin-converting enzyme inhibitors (ACEIs) reverses cerebral arteriolar remodeling, thus restoring dilatation and hence the lower limit of cerebral blood flow (CBF) autoregulation (LLCBF). The objective of this study was to determine whether angiotensin II receptor AT1 blockers (ARBs) produce the same effect.


METHODS
We examined the effects of treatment with an ARB [telmisartan (TEL), 1.93 +/- 0.04 mg/kg per day] or an ACEI [ramipril (RAM), 1.00 +/- 0.02 mg/kg per day] on the cerebral circulation in spontaneously hypertensive rats (SHR).


METHODS
Arteriolar pressure and diameter (cranial window) and CBF (laser Doppler) were measured during stepwise hypotensive hemorrhage, before and after deactivation (ethylenediamine tetraacetic acid), in untreated Wistar-Kyoto (WKY) rats and SHR untreated or treated for 3 months with TEL or RAM in the drinking water.


RESULTS
Treatment normalized arteriolar internal diameter (SHR, 38 +/- 3 microm; TEL, 52 +/- 2 microm; RAM, 50 +/- 2 microm; WKY, 58 +/- 4 microm), essentially by reversing eutrophic inward remodeling, and the LLCBF (SHR, 80 +/- 11 mmHg; TEL, 60 +/- 4 mmHg; RAM, 71 +/- 6 mmHg; WKY, 57 +/- 5 mmHg).


CONCLUSIONS
The fact that the ARB (TEL) is as effective as an ACEI (RAM) in reversing cerebral arteriolar remodeling suggests that the cerebrovascular AT1 receptor is an underlying mechanism that promotes hypertensive eutrophic inward remodeling.
Dupuis
François
F
Cardiovascular Research Group, INSERM U684, Faculté de Pharmacie, Université Henri Poincaré-Nancy I, Nancy, France.
Atkinson
Jeffrey
J
Limiñana
Patrick
P
Chillon
Jean-Marc
JM
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects* / Q000473:pathology; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D002536:Cerebral Arteries / Q000187:drug effects* / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D006706:Homeostasis; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D017257:Ramipril / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology; D000077333:Telmisartan; D014664:Vasodilation / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001565:Benzoates; D044140:Receptor, Angiotensin, Type 1; D017257:Ramipril; D000077333:Telmisartan