M1 receptors in blood pressure-controlled ischemic spontaneously hypertensive rats.
OBJECTIVE
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 alpha-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.
Hirata
H
H
Department of Neuroscience, Okayama University Medical School, Japan.
Asanuma
M
M
Tanaka
K
K
Kondo
Y
Y
Ogawa
N
N
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002560:Cerebrovascular Circulation; D002561:Cerebrovascular Disorders / Q000503:physiopathology; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006973:Hypertension / Q000517:prevention & control*; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D008297:Male; D009529:Nicardipine / Q000627:therapeutic use*; D010646:Phentolamine / Q000627:therapeutic use*; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000235:genetics
D012333:RNA, Messenger; D011976:Receptors, Muscarinic; D009529:Nicardipine; D010646:Phentolamine