Reflex hypertensive response induced by capsaicin involves endothelin-dependent mechanisms

Area of Science:

• Pharmacology
• Physiology
• Neuroscience

Background:

• Capsaicin, a known nociceptive agent, elicits complex cardiovascular and respiratory responses.
• The precise physiological mechanisms underlying capsaicin-induced pressure changes, particularly the triphasic response, remain incompletely understood.

Purpose of the Study:

• To elucidate the specific mechanisms responsible for the immediate, intermediate, and delayed phases of capsaicin-induced pressure responses in rats.
• To investigate the roles of vagal nerve activity, endothelin, nitric oxide synthase, prostaglandin synthase, and kinin synthase in these responses.

Main Methods:

• Anesthetized rats underwent cannulation of the trachea, jugular vein, and femoral artery for physiological monitoring.
• Capsaicin (10 µg/kg, i.v.) was administered to record blood pressure, respiratory excursions, and ECG.
• Experiments were conducted before and after vagotomy, and in the presence of specific antagonists: bosentan (endothelin receptor antagonist), L-NAME (nitric oxide synthase inhibitor), indomethacin (prostaglandin synthase inhibitor), and aprotinin (kinin synthase inhibitor).

Main Results:

• Capsaicin induced a triphasic pressure response: initial fall, intermediate recovery (hypertension after vagotomy), and delayed progressive fall.
• Vagotomy abolished the immediate hypotension and associated bradycardia/tachypnea, potentiated the intermediate phase into hypertension, and preserved the delayed hypotension.
• Endothelin receptor blockade (bosentan) inhibited the intermediate hypertensive response in vagotomized rats but did not affect the delayed hypotension.
• Inhibition of nitric oxide synthase, prostaglandin synthase, or kinin synthase did not alter the delayed hypotensive response.

Conclusions:

• The intermediate hypertensive response to capsaicin in rats is mediated by endothelin-dependent pathways.
• The delayed hypotensive response to capsaicin is independent of nitrergic, prostaglandinergic, and kininergic mechanisms.
• Vagal nerve activity plays a crucial role in modulating the immediate and intermediate phases of capsaicin's cardiovascular effects.