Involvement of NO and KATP channel in adenosine A2B receptors induced cardiovascular regulation in the posterior hypothalamus of rats.
Previous reports have suggested that the posterior hypothalamic adenosine A2 receptors may play a role in central cardiovascular regulation. In this study, we examined the influence of posterior hypothalamic adenosine A2B receptors on the regulation of blood pressure and heart rate. Drugs were injected into the posterior hypothalamus of anesthetized, artificially ventilated, male Sprague-Dawley rats. Four nanomoles of 5'-N-ethylcarboxamidoadenosine (NECA), an adenosine A 2A receptor agonist, decreased arterial blood pressure and heart rate, whereas 5 nmol of alloxazine, an adenosine A2B receptor antagonist, blocked the depressor and bradycardiac effects of 4 nmol NECA. We examined the role of nitric oxide (NO) and K+ channels on cardiovascular regulation by adenosine A2B receptors in the posterior hypothalamus. Pretreatment with 40 nmol of NG-nitro-L-arginine methyl ester, a NO synthase inhibitor, significantly attenuated the effects of NECA, and 10 nmol of sodium nitroprusside, a NO releaser, strengthened the action of drug. In addition, posterior hypothalamic administration of 20 nmol of glipizide, an K ATP blocker, blocked the cardiovascular depression elicited by NECA. These results suggest that NO mediates cardiovascular regulation by activation of A2B receptors in the posterior hypothalamus. Additionally, ATP-sensitive K+ channels modulate the action of adenosine A2B receptors.
Lee
Tae-Kyung
TK
Department of Pharmacology, College of Medicine, Hanyang University, Seoul, Korea.
Koh
Hyun Chul
HC
D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005415:Flavins / Q000494:pharmacology; D005913:Glipizide / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D007034:Hypothalamus, Posterior / Q000187:drug effects / Q000502:physiology*; D007097:Imines / Q000494:pharmacology; D054086:KATP Channels / Q000502:physiology*; D008297:Male; D008845:Microinjections; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043704:Receptor, Adenosine A2B / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D000634:Aminoquinolines; D004791:Enzyme Inhibitors; D005415:Flavins; D007097:Imines; D054086:KATP Channels; D043704:Receptor, Adenosine A2B; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D019830:Adenosine-5'-(N-ethylcarboxamide); C008173:isoalloxazine; C014925:RMI 12330A; C041715:6-anilino-5,8-quinolinedione; D019331:NG-Nitroarginine Methyl Ester; D005913:Glipizide