Adenosine receptor subtypes in the brainstem mediate distinct cardiovascular response patterns.

摘要: A limited occipital craniotomy was conducted on urethane-chloralose anesthetized, spontaneously breathing rats to expose the caudal medulla in region of obex. Microinjections highly selective agonists for adenosine receptor subtypes were made into medial nucleus tractus solitarius (NTS) at level posterior portion area postrema. Cardiorespiratory parameters subsequently recorded a 60-min test period following microinjection drug or vehicle solutions. The used: A1 agonist, N6-cyclopentyladenosine (CPA), which is 480-fold receptors rat brain binding assays, and A2 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680), 170-fold studies over 1500-fold functional assays. results showed that distinct converse cardiovascular response patterns elicited by these microinjections NTS. Specifically, CGS 21680 selectively potent dose-related decreases mean arterial blood pressure (ED50 = 0.064 nmol/kg) pulse (ED50= 0.058 nmol/kg). Conversely, CPA increases 0.62 0.70 Additionally, overall agonist-mediated dramatically different wherein agonist exhibited considerably more rapid time course eliciting its hypotensive responses whereas delayed substantially longer exert hypertensive responses. further shown be receptor-selective since depressor 21680, pressor CPA, completely blocked, respectively, antagonist, 15943A, DPCPX. Taken together, findings provide persuasive vivo evidence showing pharmacologic activation NTS elicits specific with opposite actions cardiorespiratory behavior. These data also indicate separate physiologic are specifically mediated intact nervous system thereby lend additional support case using models assess role function.