RESUMEN
The objective of this study was to test the hypothesis that fentanyl induces a depressor response in the pulmonary vascular bed of the cat and to identify the receptors involved in the mediation or modulation of these effects. The authors conducted a prospective vehicle-controlled study at a university research laboratory using intact chest preparation in adult mongrel cats. In separate experiments, the effects of diphenhydramine (histamine receptor blocker), glibenclamide (ATP-sensitive K+ channel blocker), L-N5-(1-Iminoethyl) ornithine hydrochloride (L-NIO) (nitric oxide synthase inhibitor), nimesulide (selective cyclooxygenase [COX]-2 inhibitor), and naloxone (opiate receptor antagonist) were investigated on pulmonary arterial responses to fentanyl and other agonists in the pulmonary vascular bed of the cat. The systemic pressure and lobar arterial perfusion pressure were continuously monitored, electronically averaged, and recorded. In the feline pulmonary vascular bed of the isolated left lower lobe, fentanyl induced a dose-dependent vasodepressor response that was not significantly altered after administration of glibenclamide, L-NIO, and nimesulide. However, the responses to fentanyl were significantly attenuated after administration of diphenhydramine and naloxone. The results of the present study suggest that fentanyl has potent vasodepressor activity in the pulmonary vascular bed of the cat and that this response may be mediated or modulated by both histaminergic and opiate receptor sensitive pathways.
Asunto(s)
Fentanilo/farmacología , Arteria Pulmonar/efectos de los fármacos , Receptores Opioides/efectos de los fármacos , Vasodilatación/efectos de los fármacos , Vasodilatadores/farmacología , Analgésicos Opioides/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Bradiquinina/metabolismo , Gatos , Ciclooxigenasa 2/metabolismo , Difenhidramina/farmacología , Relación Dosis-Respuesta a Droga , Histamina/metabolismo , Antagonistas de los Receptores Histamínicos H1/farmacología , Naloxona/farmacología , Antagonistas de Narcóticos/farmacología , Óxido Nítrico/metabolismo , Norepinefrina/metabolismo , Arteria Pulmonar/metabolismo , Circulación Pulmonar/efectos de los fármacos , Receptores Opioides/metabolismoRESUMEN
OBJECTIVE: The purpose of this study was to test the hypothesis that meperidine induces a dilator response in the feline pulmonary vascular bed, and to identify receptors involved in the mediation or modulation of these effects. DESIGN: Prospective vehicle controlled study. SETTING: University research laboratory. SUBJECTS: Intact chest preparation; adult mongrel cats. INTERVENTIONS: In separate experiments, the effects of diphenydramine (histamine H(1)-receptor antagonist), glibenclamide (adenosine triphosphate-sensitive K+ channel blocker), L-N(5)-(1-Iminoethyl) ornithine hydrochloride (L-NIO) (nitric oxide synthase inhibitor), naloxone (opioid receptor antagonist), and nimesulide (selective cyclooxygenase-2 inhibitor) were investigated on pulmonary arterial responses to meperidine and other agonists in the feline lung bed. MEASUREMENTS AND MAIN RESULTS: The systemic pressure and lobar arterial perfusion pressure were continuously monitored, electronically averaged, and permanently recorded. Under elevated tone conditions in the isolated left lower lobe vascular bed of the cat, meperidine induced a dose-dependent vasodilator response that was not significantly altered after administration of glibenclamide, L-NIO, and nimesulide. Responses to meperidine were significantly attenuated after the administration of diphenydramine and naloxone. CONCLUSIONS: The results suggest that meperidine has potent vasodilator activity in the feline pulmonary vascular bed, and these responses are mediated or modulated, in part, by opioid and histamine receptor-sensitive pathways.
Asunto(s)
Analgésicos Opioides/farmacología , Meperidina/farmacología , Arteria Pulmonar/efectos de los fármacos , Venas Pulmonares/efectos de los fármacos , Presión Esfenoidal Pulmonar/fisiología , Vasodilatación/fisiología , Animales , Gatos , Femenino , Estudios de Seguimiento , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/prevención & control , Hipertensión Pulmonar/veterinaria , Masculino , Pronóstico , Estudios Prospectivos , Arteria Pulmonar/fisiología , Venas Pulmonares/fisiología , Presión Esfenoidal Pulmonar/efectos de los fármacos , Vasodilatación/efectos de los fármacosRESUMEN
The purpose of this prospective vehicle controlled study was to test the hypothesis that sufentanil induces a depressor response in the pulmonary vascular bed of the cat and identify the receptors involved in the mediation or modulation of these effects. In separate experiments, the effects of diphenydramine (histamine receptor blocker), glibenclamide (ATP-sensitive K+ channel blocker), L-N5-(1-Iminoethyl) ornithine hydrochloride (L-NIO) (nitric oxide synthase inhibitor), nimesulide (selective cyclooxygenase (COX)-2 inhibitor), and naloxone (opiate receptor antagonist) were investigated on pulmonary arterial responses to sufentanil and other agonists in the feline pulmonary vascular bed. The lobar arterial perfusion pressures were continuously monitored, electronically averaged, and recorded. In the feline pulmonary vascular bed of the isolated left lower lobe, sufentanil induced a dose-dependent vasodepressor response that was not significantly altered after administration of glibenclamide, L-NIO, and nimesulide. However, the responses to sufentanil were significantly attenuated following administration of diphenhydramine and naloxone. The results of the present study suggest that sufentanil has potent vasodepressor activity in the pulmonary vascular bed of the cat and that this response may be mediated or modulated by both histaminergic and opioid receptor sensitive pathways.