Subthreshold Doses of Inflammatory Mediators potentiate One Another to Elicit Reflex Cardiorespiratory Responses in Anesthetized Rats

BACKGROUND: Reflex cardio-vascular and respiratory (CVR) alterations evoked by intraarterial instillation of nociceptive agents are termed vasosensory reflexes. Such responses elicited by optimal doses of inflammatory mediators have been described in our earlier work. OBJECTIVE: The present study was designed to evaluate the interactions between subthreshold doses of inflammatory mediators on perivascular nociceptive afferents in urethane anesthetized rats. METHODS: Healthy male adult rats (Charles-Foster strain) were anesthetized with an intraperitoneal injection of urethane. After anesthesia, the right femoral artery was cannulated. Respiratory movements, blood pressure, and electrocardiogram were recorded. The interactions between subthreshold doses of algogens in the elicitation of vasosensory reflex responses were studied by instillation of bradykinin (1 nM) and histamine (100 μM) into the femoral artery one after the other, in either temporal combination in separate groups of rats. The CVR responses obtained in these groups were then compared with the responses produced by 100 μM histamine and 1 nM bradykinin in saline-pretreated groups, which served as control. RESULTS: Subthreshold doses of histamine elicited transient tachypnoeic, hyperventilatory, hypotensive, and bradycardiac responses, in rats pretreated with subthreshold doses of bradykinin [p < 0.01, two-sided Dunnett's test] but not in saline pretreated groups [p > 0.05, two-sided Dunnett's test]. Similar responses were elicited by bradykinin after histamine pretreatment compared to the saline-pretreated group. Furthermore, CVR responses produced by histamine in the bradykininpretreated group were greater in magnitude as compared to bradykinin-induced responses in the histamine-pretreated group [p < 0.05, two-sided Dunnett's test]. CONCLUSION: The present study demonstrates that both bradykinin and histamine potentiate one another in the elicitation of vasosensory reflex responses, and bradykinin is a better potentiator than histamine at the level of perivascular nociceptive afferents in producing reflex CVR changes.