Effects of an angiotensin-converting enzyme inhibitor and a beta-blocker on cerebral arteriolar dilatation in hypertensive rats.
We examined the effects of the angiotensin-converting enzyme inhibitor perindopril and the beta-blocker propranolol on dilator responses of cerebral arterioles in chronic hypertension. Dilator responses to acute hypotension were examined in untreated Wistar-Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) that were untreated or treated for 3 months with a low (0.3 mg. kg(-1). day(-1)) or a high (2 mg. kg(-1). day(-1)) dose of perindopril or a dose of propranolol (250 mg. kg(-1). day(-1)) alone or in combination with the low dose of perindopril. Pressure (servo-null) and diameter were measured in cerebral arterioles during acute reductions in arterial pressure both before and during maximal dilatation (EDTA). The high dose of perindopril or the combination of propranolol and perindopril normalized cerebral arteriolar pressure (52+/-2 [mean+/-SEM], 49+/-2 mm Hg versus 50+/-2 mm Hg in WKY and 96+/-3 mm Hg in untreated SHRSP; P<0.05). In contrast, the low dose of perindopril or propranolol alone did not normalize arteriolar pressure (74+/-2 mm Hg and 58+/-3 mm Hg). Both the low and high doses of perindopril improved autoregulatory dilatation, maximal dilatation, and dilator reserve of cerebral arterioles in SHRSP, with the low dose of perindopril being almost as effective as the high dose of perindopril. Propranolol alone did not significantly improve dilator function of cerebral arterioles. Furthermore, dilator function of cerebral arterioles was not further improved by the addition of propranolol to the low dose of perindopril. These findings suggest that angiotensin-converting enzyme inhibitors, such as perindopril, may be more effective than propranolol in attenuating the impairment of cerebral autoregulatory vasodilatation, maximal dilatation, and dilator reserve during treatment of chronic hypertension.
Chillon
J M
JM
Cardiovascular Research Group, Faculty of Pharmacy, University of Nancy, Nancy, France. chillon@pharma.u-nancy.fr
Baumbach
G L
GL
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002536:Cerebral Arteries / Q000187:drug effects* / Q000473:pathology; D002908:Chronic Disease; D004108:Dilatation, Pathologic / Q000188:drug therapy; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D020913:Perindopril / Q000627:therapeutic use*; D011433:Propranolol / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D011433:Propranolol; D020913:Perindopril