この研究は、脳卒中抵抗性高血圧自然発症ラットを用い、それらが高血圧発症中に、中程度の強度の静磁界（SMF）とL型電圧依存性カルシウムチャネル遮断薬であるニカルジピンの組み合わせばく露を与え、その効果を測定した。SMFばく露用の円板型永久磁石またはダミー磁石を、各ラットの頸部の左頸動脈洞圧受容器付近に植え込み、その最大磁束密度は180 mT、ピーク空間勾配133 mT/ mmであった。最大ばく露期間は14週間とした。5週齢の雄ラットをそれぞれ14匹からなる4群に分けた；（1）生理食塩水の腹腔内投与＋SMFの擬似ばく露（対照群）、（2）生理食塩水の腹腔内投与＋SMFばく露（SMF群）、（3）ニカルジピンの腹腔内投与＋SMFの擬似ばく露（NIC群）、（4）ニカルジピンの腹腔内投与＋SMFばく露（SMF + NIC群）。生理食塩水またはニカルジピンを週に3回、14週間投与し、その15分後に、動脈血圧（BP）、心拍数（HR）、圧反射感度（BRS）、皮膚血流量（SBF）、皮膚血流速度（SBV）、血漿中の一酸化窒素（NO）代謝物、血漿カテコールアミンレベル、さらには機能観察用バッテリーによる行動パラメータを測定した。その結果、対照群に比べ、NIC群では、ニカルジピンの作用で、血漿NO（x）レベルを変化させることなく、BPの有意な低下、HR、SBF、SBV、血漿エピネフリンおよびノルエピネフリンの有意な上昇が見られた；5-8週間のSMF単独ばく露により、SMF群において、BRS上昇とともに高血圧の発症が有意に抑制または遅延された；1-8週間のSMFばく露によって、NIC群に比べ、SMF + NIC群でのニカルジピン誘発BP低下が有意に促進された；また、SMFは、ニカルジピン誘発性低血圧症における血漿NO（x）の有意な増加を誘発した；SMF + NIC群とNIC群の間、またはSMF群と対照群の間に、生理学的または行動パラメータのいずれにも有意な差はなかった、と報告している。
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To examine the hypothesis that a moderate intensity static magnetic field may influence Ca2+ dynamics in nicardipine (a voltage-gated Ca2+ ion channel blocker)-induced hypotensive SHR (spontaneously hypertensive rat) and modulate reduced blood pressure. This investigation was designed to evaluate the effects of local application of the moderate intensity static magnetic field on pharmacologically modulated blood pressure in the development of genetic hypertension and to elucidate how the static magnetic field influences cardiovascular parameters and Ca2+-related biological pathways and responses.
Four experimental groups of 14 animals each were examined: (1) sham exposure with saline injection (control); (2) static magnetic field exposure with saline injection; (3) sham exposure with nicardipine injection; (4) static magnetic field exposure with nicardipine injection.
Nicardipine (2 mg/kg) was administered three times a week for 14 weeks, and then 15 min after each injection measurements were performed.
Four experimental groups of 14 animals each were examined: (1) sham exposure with intraperitoneal (ip) saline injection control);(2) SMF exposure with ip saline injection (SMF); (3) sham exposure with ip nicardipine injection (NIC); (4) SMF exposure with ip nicardipine injection.
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| ばく露時間 | continuous for 14 weeks |
| ばく露の発生源／構造 |
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| ばく露装置の詳細 | The magnet was surgically implanted in the vicinity adjacent to the left carotid sinus baroreceptor region in the neck. As sham exposed controls, a dummy magnet of the same size, weight, and material as the real magnet was implanted in the same position of each rat . The surfaces of both real and dummy magnets were coated with PTFE (Teflon) to use biomedical implant. |
| Additional information | The north side of the magnet was oriented towards the left carotid artery and the nearest distances from the edge of the magnet to the left carotid sinus were 2-3 mm. The principal axis of the left carotid artery was directed perpendicular to the SMF. |
The action of nicardipine significantly decreased blood pressure, and increased heart rate, skin blood flow, skin blood velocity, plasma epinephrine and norepinephrine in the nicardipine group compared with the control group without changing plasma nitric oxide metabolite levels.
Local application of a moderate intensity static magnetic field for 5-8 weeks suppressed or delayed the blood pressure elevation in SHR. The static magnetic field acted synergistically with nicardipine-induced hypotension during 1-8 week exposure periods. Moreover, the static magnetic field induced a significant increase in plasma nitric oxide in the nicardipine-induced hypotension.
These findings indicate that the static magnetic field may enhance nicardipine-induced hypertension by more effectively antagonizing the Ca2+ influx through the Ca2+ channels compared with the nicardipine treatment alone. Furthermore, the enhanced antihypertensive effects of the static magnetic field on the nicardipine-treated rats may be partially related to increased nitric oxide metabolite levels.
Theoretical considerations suggest that the applied static magnetic field can be converted into a changing magnetic field in the baroreceptor region by means of the carotid artery pulsation. The authors propose that the moderate intensity changing magnetic field modulated by the changing pulse rate may influence the activity of baroreceptor and baroreflex function.
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