A study to investigate capsaicin-induced pressure response in vagotomized rats

Abstract

Objectives: Capsaicin is used to evoke pulmonary C reflexes and produces complex pressure responses along with apnea/tachypnea, and bradycardia. In the present study, the mechanisms involved in capsaicin-induced pressure responses were explored.

Materials and methods: Tracheal, jugular venous, and femoral artery cannulations were performed in anesthetized adult rats. Blood pressure, respiratory excursions, and electrocardiogram were recorded. Cardiorespiratory reflex changes evoked by jugular venous injection of capsaicin (10 μg/kg) were recorded in vagotomized and antagonist pretreated animals.

Results: Capsaicin produced triphasic pressure response exhibiting immediate hypotension, intermediate recovery, and delayed hypotension. Time-matched respiratory changes showed apnea, bradypnea, and tachypnea, respectively. Bradycardia occurred at immediate and intermediate phases. After vagotomy, immediate hypotension was abolished; the intermediate recovery was potentiated as hypertensive response; and the delayed hypotension persisted. In case of respiration, the immediate bradypnea persisted and delayed tachypnea was abolished; while heart rate changes at immediate and intermediate phases were abolished. Antagonists of α1-adrenoceptor (prazosin or terazosin, 0.5 mg/kg), β-adrenoceptor (propranolol, 1 mg/kg), AT1 receptor (losartan, 10 mg/kg) and Ca(2+) channel (diltiazem, 1 mg/kg) failed to block the capsaicin-induced intermediate hypertensive response in vagotomized animals.

Conclusions: These observations implicate the existence of mechanisms other than adrenergic, angiotensinergic, or Ca(2+) channel-dependent mechanisms for mediating the capsaicin-induced intermediate hypertensive response in vagotomized animals.

Keywords: Adrenoceptor antagonist; capsaicin; diltiazem; losartan; prazosin; propranolol.

Figure 1

Capsaicin-induced cardiorespiratory responses before and after vagotomy. The original tracings of an experiment showing the capsaicin (10 μg/kg)-induced changes in blood pressure (BP); respiration (Resp); and heart rate (ECG), before and after vagotomy are presented in the left panel. Vertical dashed line indicates the point of injection of capsaicin (10 μg/kg). Horizontal line (time scale) = 5 s. Recording of BP at 10 times slower speed is shown in inset A and B for before and after vagotomy, respectively. In inset A, the triphasic BP response (immediate hypotension, intermediate recovery, and delayed hypotension) after capsaicin is shown and in inset B, the potentiation of intermediate hypertensive response is indicated by an arrow. The mean ± SEM values (n= 12) of MAP, RF, and HR as % of initial at immediate (Immed), intermediate (Inter), and delayed phases are presented in the bar diagrams. * (P< 0.05, Student's t-test for paired observations)

Figure 2

The original tracings of blood pressure (BP), respiration (Resp), and electrocardiogram (ECG) before, after vagotomy and after prazosin in vagotomized animals are presented on the left. Vertical dashed line indicates the point of capsaicin administration. Horizontal line (time scale) = 5 s for all. The mean ± SEM values (n = 3) of MAP, RF, and HR at immediate (Immed), intermediate (Inter), and delayed phases are presented in the bar diagrams. Before indicates before vagotomy; + VagX indicates after vagotomy; and + Prazosin indicates prazosin after vagotomy. * (P < 0.05, One-way ANOVA followed by Student-Newman-Keuls test).

Figure 3

The original tracings of BP, respiration (Resp), and ECG before, after vagotomy and after propranolol in vagotomized animals are presented on the left. Vertical dashed line indicates the point of capsaicin administration. Horizontal line (time scale) = 5 s for all. The mean ± SEM values (n = 3) of MAP, RF, and HR at immediate (Immed), intermediate (Inter), and delayed phases are presented in the bar diagrams. Before indicates before vagotomy; + VagX indicates after vagotomy; and + Propran indicates propranolol after vagotomy. *(P < 0.05, One-way ANOVA followed by Student- Newman-Keuls test).

Figure 4

The original tracings of BP, respiration (Resp), and ECG before, after vagotomy and after losartan in vagotomized animals are presented on the left. Vertical dashed line indicates the point of capsaicin administration. Horizontal line (time scale) = 5 s for all. The mean ± SEM values (n = 4) of MAP, RF, and HR at immediate (Immed), intermediate (Inter), and delayed phases are presented in the bar diagrams. Before indicates before vagotomy; + VagX indicates after vagotomy; and + Losart indicates losartan after vagotomy. (*) indicates significant difference from the before values at each phase (P < 0.05, One-way ANOVA followed by Student-Newman-Keuls test)

Figure 5

The original tracings of BP, respiration (Resp), and ECG before, after vagotomy and after diltiazem in vagotomized animals are presented on the left. Vertical dashed line indicates the point of capsaicin administration. Horizontal line (time scale) = 5 s for all. The mean ± SEM values (n = 3) of MAP, RF, and HR at immediate (Immed), intermediate (Inter), and delayed phases are presented in the bar diagrams. Before indicates before vagotomy; + VagX indicates after vagotomy; and + Dilt indicates diltiazem after vagotomy. *(P< 0.05, One-way ANOVA followed by Student-Newman-Keuls test)