This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Hirata, H. Articles by Ogawa, N. Search for Related Content PubMed PubMed Citation Articles by Hirata, H. Articles by Ogawa, N.

(Stroke. 1995;26:1268-1272.)
© 1995 American Heart Association, Inc.

Articles

M1 Receptors in Blood Pressure–Controlled Ischemic Spontaneously Hypertensive Rats

Hiroshi Hirata, MD, PhD; Masato Asanuma, MD, PhD; Ken-ichi Tanaka, MSc; Yoichi Kondo, MD Norio Ogawa, MD, DMSc

From the Department of Neuroscience, Institute of Molecular and Cellular Medicine (H.H., M.A., K.T., Y.K., N.O.), and the Third Department of Internal Medicine, Okayama University Medical School (H.H., Y.K.), Okayama, Japan.

Correspondence to Norio Ogawa, MD, DMSc, Department of Neuroscience, Institute of Molecular and Cellular Medicine, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700, Japan.

Background and Purpose Hypertension is a primary aggravating factor in cerebral infarction. An acute rise in blood pressure (BP) at the time of a stroke may be harmful to the brain in a hypertensive subject because both cerebral vascular structure and function are altered by hypertension. Muscarinic M₁ receptors are concerned with memory and learning. We aimed to evaluate the effect of controlling BP in hypertensive subjects at the time of stroke with a biochemical index of brain damage.

Methods We gave a single dose of either the antihypertensive -blocker phentolamine (2 mg/kg IP) or the calcium antagonist nicardipine (2 mg/kg IP) at the start of bilateral carotid artery occlusion to spontaneously hypertensive rats undergoing 3 hours of transient ischemia; we measured the time course of mean BP (MBP) and changes in the M₁ receptor and its mRNA in three brain regions 2 weeks after the transient ischemia.

Results Administration of phentolamine or nicardipine not only significantly suppressed the ischemia-induced rise of MBP, it actually decreased MBP during ischemia. In an ischemic control group, M₁ receptor binding decreased in the frontal cortex and M₁ receptor mRNA increased in the hippocampus 2 weeks after the ischemia. In contrast, both phentolamine- and nicardipine-treated ischemic rats showed no changes in either index compared with sham-operated controls.

Conclusions Controlling BP during an ischemic insult attenuates ischemia-induced damage of M₁ receptors in the brain of spontaneously hypertensive rats. These results suggest that a rapid intensive increase of BP at the time of a stroke may exacerbate brain damage in hypertensive individuals.

Key Words: calcium channel blockers • cerebral ischemia • hypertension • rats