高血圧ラット（SHR）における長期降圧治療の脳虚血発症に及ぼす影響—塩酸ニカルジピン投与の効果

INFLUENCE OF LONG-TERM ANTIHYPERTENSIVE TREATMENT ON CEREBRAL ISCHEMIA INDUCED BY BLCL IN SHRSR:PROTECTIVE EFFECT OF NICARDIPINE HYDROCHLORIDE

　抄録　Ca拮抗薬である塩酸ニカルジピンを高血圧ラットのSHRSRに長期投与し，両側総頸動脈結紮（BLCL）による脳虚血を作成し，脳虚血の発症程度について脳代謝諸量（ATP, lactate, c-AMP），脳浮腫および脳血管における電顕所見を検討し，未治療のSHRSRと比較し，長期降圧治療が脳虚血発症に及ぼす影響について検索した。脳代謝諸量では，降圧治療群は未治療群に比しATP値，c-AMP値において有意に高値を示し，lactate値では有意に低値を示し，脳代謝障害の程度は軽度であった。脳含水量においても降圧治療群は未治療群に比べて有意に低値を示し，脳浮腫の程度も軽度であった。脳血管における電顕所見では，治療群は未治療群に比べ血管収縮や虚血時に血管内腔に出現するmicrovilliの増生は認められず，虚血性変化は軽度であった。以上より，Ca拮抗薬投与によるSHRSRの長期降圧治療は，BLCL後の脳虚血発症の程度を軽減させ得ることが示された。

We have already reported that the long-term antihypertensive treatment reduced the degree of cerebral ischemia induced by bilateral common carotid artery ligation (BLCL) in stoke- resistant spontaneously hypertensive rats (SHRSR). This antihypertensive treatment was achieved by the combination of captopril and hydroflumethiazide.

In this study, nicardipine hydrcchloride which is one of the Ca²⁺ antagonist was similarly admi-nistrated to SHRSR for 8-10 weeks (T-SHR). The effect of long-term antihypertensive treatment by this agent on cerebral ischemia induce by BLCL was investigated and compared with untreated SHRSR (U-SHR). The degree of cerebral ischemia 4 hr after BLCL was estimated by the levels of brain energy metabolites (ATP, lactate, c-AMP) and brain water content. The brain metabolites and water content were measured in the fcrebrain and hindbrain of each hemisphere. And also the histopathological study on brain vessels 3hr after BLCL was achieved by using scanning electron microscopy (SEM).

The blood pressure of T-SHR gradually de-clined from 185±10 mmHg (mean±S.D.) to 154± 8 mmHg after 8-10 weeks of antihypertensive treatment. However the blood pressure of U-SHR spontaneously changed from 185±8 mmHg to 206 ±12 mmHg after 8-10 weeks. The blood pressure of T-SHR after the treatment was significantly lower than that of U-SHR. The levels of ATP and c-AMP in T-SHR after BLCL were statisti-cally higher than those in U-SHR, and the lac-tate levels in T-SHR were significantly lower than in U-SHR in the both fore- and hindbrain. The brain water conent of T-SHR in the both regions was significantly lower than U-SHR after BLCL. From the observetion of SEM study in brain vessels after BLCL, a large number of mic-rovilli on the endothelial surface and vasoconst-riction were observed in U-SHR. On the other hand, these vascular endothelial ischemic changes were not shown, and the marginal folds were observed to remain in T-SHR even after BLCL.

These observations indicated that the long-term antihypertensive treatment by nicardipine hydro-chloride contributed to the ameliorating effect on ischemic insult as well as the combination treat-ment of captopril and hydroflumethiazide.