Capsaicin-sensitive primary afferents are involved in the hypotensive effect of neurotensin in ganglion-blocked guinea pigs.
The mechanism of the blood pressure (BP)-lowering effect of neurotensin (NT) in the anesthetized, ganglion-blocked guinea pigs was further examined using animals in which the basal BP was artificially raised by an IV infusion of noradrenaline (NA) to overcome the BP-lowering effect of the anesthesia as well as of the ganglion blocker. The animals were also vagotomized and given atropine at the beginning of the experiments to prevent potential baroreceptor-mediated vagal reflexes and/or activation of muscarinic receptors by endogenous acetylcholine. Under these experimental conditions, the IV bolus injections of NT as well as of capsaicin (a reference drug) produced dose-dependent hypotensive effects and variable levels of tachycardia. Omitting the ganglion blocker from the animal drug regimen attenuated but did not abolish the BP-lowering effect of NT and of capsaicin. Neither the hypotensive nor the tachycardic effects of NT and of capsaicin in ganglion-blocked guinea pigs were affected by prior animal treatment with propranolol (a beta adrenoceptor blocker), antihistaminics (mepyramine, cimetidine) or indomethacin (a cyclooxygenase inhibitor). Morphine was found to slightly reduced the hypotensive effect of NT without altering its slight tachycardic effect. Both the hypotensive and tachycardic effects of NT and of capsaicin, in contrast to those elicited by substance P (SP) and calcitonin gene-related peptide (CGRP), were inhibited in ganglion-blocked guinea pigs pretreated four days previously with capsaicin.(ABSTRACT TRUNCATED AT 250 WORDS)
Rioux
F
F
Nephrology-Pharmacology and Hypertension Unit, Hôtel-Dieu de Québec, Canada.
Lemieux
M
M
Roy
G
G
D000344:Afferent Pathways / Q000187:drug effects*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology*; D005260:Female; D005725:Ganglia, Autonomic / Q000187:drug effects / Q000502:physiology*; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D007262:Infusions, Intravenous; D008297:Male; D009496:Neurotensin / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D010425:Pentolinium Tartrate / Q000494:pharmacology; D015203:Reproducibility of Results; D013373:Substance P / Q000494:pharmacology; D014628:Vagotomy
D013373:Substance P; D009496:Neurotensin; D001285:Atropine; D010425:Pentolinium Tartrate; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D009638:Norepinephrine