Interaction of Cholinergic and Cannabinoidergic Systems in Hemorrhagic Hypotension

Öz

Given the cardiovascular effects of the cholinergic and cannabinoid systems, the present study aimed to investigate the interaction of both systems in hemorrhagic hypotensive conditions. Adult male Sprague Dawley albino rats were used in the study. Under sevoflurane anesthesia, the animals were catheterized in the left carotid arteries and jugular vein for monitoring cardiovascular parameters and producing hemorrhagic hypotension and intravenous (IV) injection, respectively. The hypotension was achieved by withdrawing a total volume of 2.2 mL blood/100g body weight over 10 minutes. The hemorrhage produced a severe and long-lasting decrease in mean arterial pressure (MAP). The IV injection of rimonabant (cannabinoid CB1 receptor antagonist) and DMSO promptly and significantly increased the MAP in the hypotensive rats. When administered at a sub-effective dose CDP-choline showed a slight increase in the MAP. However, when this same dose of CDP-choline was co-administered with DMSO, it elicited a more pronounced and prolonged increase in the MAP compared to the effects observed with CDP-choline or DMSO alone. Rimonabant partially inhibited the MAP-increasing effect of the sub-effective dose of CDP-choline administered with DMSO in the hypotensive rats. These findings suggest that CDP-choline demonstrates a synergistic interaction with DMSO, resulting in a heightened and prolonged increase in MAP during hemorrhagic hypotension. Conversely, it exhibits an antagonistic interaction with rimonabant in terms of their effects on MAP under similar conditions. These results can be interpreted as indicative of an interaction between cannabinoid CB1 receptors and the cholinergic system in the hemorrhagic hypotensive condition.

Anahtar Kelimeler

• Cannabinoid CB1 receptors
• Cardiovascular system
• CDP-choline
• Hemorrhagic hypotension

Hemorajik Hipotansiyonda Kolinerjik ve Kannabinoiderjik Sistemlerin Etkileşimi

Öz

Kolinerjik ve kannabinoiderjik sistemlerin kardiyovasküler sistem üzerindeki etkileri göz önünde bulundurularak, bu çalışmada her iki sistemin hemorajik hipotansiyon koşullarındaki etkileşiminin araştırılması amaçlanmıştır. Çalışmada erişkin erkek Sprague Dawley albino sıçanlar kullanılmıştır. Sevofluran anestezisi altında, hayvanlara kardiyovasküler parametrelerin izlenmesi, hemorajik hipotansiyon oluşturulması ve intravenöz (IV) enjeksiyon uygulamaları için sırasıyla sol karotis artere ve juguler vene kateter yerleştirilmiştir. Hipotansiyon, 10 dakika içinde 100 gram vücut ağırlığı başına toplam 2,2 ml kan alınarak oluşturulmuştur. Kan alma sonucunda ortalama arter basıncında (MAP) şiddetli ve uzun süreli bir düşüş meydana gelmiştir. Rimonabant (kannabinoid CB1 reseptör antagonisti) ve DMSO'nun IV enjeksiyonu, hipotansif sıçanlarda MAP’ı hızlı ve anlamlı şekilde artırmıştır. Sub-efektif dozda uygulanan CDP-kolin, MAP’ta hafif bir artış göstermiştir. Ancak bu doz CDP-kolin DMSO ile birlikte uygulandığında, CDP-kolin veya DMSO’nun tek başına oluşturduğu etkilere kıyasla daha belirgin ve uzun süreli bir MAP artışı meydana gelmiştir. Rimonabant, hipotansif sıçanlarda DMSO ile birlikte uygulanan sub-efektif doz CDP-kolinin MAP artırıcı etkisini kısmen engellemiştir. Bu bulgular, CDP-kolinin DMSO ile sinerjistik bir etkileşim göstererek hemorajik hipotansiyon sırasında MAP’ta daha güçlü ve uzun süreli bir artış sağladığını ortaya koymaktadır. Öte yandan, benzer koşullar altında CDP-kolin ile rimonabant arasında MAP üzerindeki etkiler açısından antagonistik bir etkileşim bulunduğu görülmektedir. Bu sonuçlar, hemorajik hipotansiyon koşullarında kannabinoid CB1 reseptörleri ile kolinerjik sistem arasında bir etkileşim olduğuna işaret edebilir.

Anahtar Kelimeler

• Kannabinoid CB1 reseptörleri
• Kardiyovasküler sistem
• CDP-kolin
• Hemorajik hipotansiyon

Kaynakça

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