Title:Subthreshold Doses of Inflammatory Mediators potentiate One Another to
Elicit Reflex Cardiorespiratory Responses in Anesthetized Rats
Volume: 22
Issue: 1
Author(s): Ravindran Revand, Sanjeev K. Singh*Madaswamy S. Muthu
Affiliation:
- Department of Physiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, UP, India
Keywords:
Bradykinin, histamine, potentiation, subthreshold, vasosensory reflexes, nociception, algogens, perivascular.
Abstract:
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.
