Letter to the Editor Mechanisms underlying the hypertensive response induced by capsaicin Abhaya Dutta, Shripad B. Deshpande ⁎ Department of Physiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi-221005, India abstract article info Article history: Received 14 December 2009 Accepted 13 February 2010 Available online xxxx Keywords: α-adrenoceptor AT1 receptor Capsaicin Endothelin Hypertensive crisis Acute ingestion of large quantity of chili peppers (rich source of capsaicin) produced hypertensive crisis in a patient. The hypertensive response was explained on the basis of decreased vasodilator substance calcitonin gene-related peptide (CGRP) from sensory nerve terminals by capsaicin. Here we present our experimental observations in anaesthetized rats regarding the mechanisms underlying hypertensive response induced by capsaicin. Our results demonstrate non-involvement of adrenergic and angiotensinergic mechanisms and also the cardiac changes in producing the response. Thus, the direct action of capsaicin on vascular smooth muscle or the activation of endothelin is proposed. © 2010 Published by Elsevier Ireland Ltd. 1. Introduction In a recent case report, patient consuming pepper in a large quantity manifested with hypertensive crisis [2]. Pepper contains an active ingredient, capsaicin and the hypertensive crisis in this report has been attributed to it. They explained the phenomenon on the basis of the depletion of vasodilator calcitonin gene-related peptide (CGRP) from C fibres by capsaicin. The patient exhibited very high systolic pressure which can also be mediated by adrenergic, angiotensinergic or cardiogenic mechanisms. Therefore, we present here our experimental observations in anaesthetized rats which provide the basis for possible explanations of capsaicin- induced hypertensive response. 2. Methods and Results The experiments were performed on adult rats of Charles Foster strain (∼ body weight: 200 g). After urethane anaesthesia trachea, jugular vein and femoral artery were cannulated. Blood pressure was recorded by connecting Stathum transducer to the femoral artery. ECG potentials were recorded by needle electrodes in standard limb lead II configuration. Capsaicin (10 μg/kg) was injected via jugular vein and the ECG and blood pressure were recorded on a chart recorder. Our observations (Fig. 1) reveal that injection of capsaicin (10 μg/kg, i.v.) in anaesthetized rats (n = 6) produced hypotensive response (-60 ± 5.4 mm Hg from initial) followed by hypertensive response (+ 29 ± 9.2 mm Hg from initial) associated with bradycardia. The latency for hypotensive response was 2 s and for hypertensive response was 6 s. The bradycardia was greater with hypotensive response (108 ± 24.5 bpm) than with hypertensive response (126 ± 38.7 bpm) as against the initial heart rate (244 ± 27.1 bpm). The hypertensive response was not abolished in animals after bilateral vagotomy (n =6) rather it was augmented by 2 times (Fig. 1). Neither prazosin (α 1 -adrenoceptor antagonist; n =3) nor losartan (AT 1 -receptor antagonist; n =3) pretreatment blocked the hypertensive response. 3. Discussion Capsaicin-induced hypertensive response can be mediated by decreased vasodilatation (CGRP, kinin or prostaglandin) or increased vasoconstriction (catecholamines, angiotensin or endothelin) or by enhanced cardiac activity (rate and force). The present study excludes the involvement of adrenergic and angiotensinergic vasoconstrictive mechanisms. Further, it reveals that the hypertension is not related to heart rate as hypertensive response persisted with bradycardia. This is further supported by the vagotomy data, where bradycardia was not observed but there was augmentation (2 times) of hypertensive response (Fig. 1). In addition, our observations demonstrate that the hypertensive response is not reflexly mediated unlike the hypotensive response. Our assumption for the involvement of α 1 adrenoceptor for the hypertension was ruled out as prazosin pretreatment did not block the hypertensive response. This is in agreement with the earlier observations, where the hypertensive response was not attenuated in spinalized rats injected with capsaicin indicating the non-involvement of medullary sympathetic drive [1]. Angiotensin-II is another potent vasoconstrictor that can be involved in the capsaicin-induced hypertension but our results exclude that possibility because losartan (AT 1 -receptor antagonist) failed to block the response. In a report elsewhere, direct action of capsaicin on smooth muscle was speculated [4]. Thus, the hypertensive effect may be due to the direct action of capsaicin as discussed earlier [4]. Recently capsaicin is shown to release endothelin from sensory nerve terminals [3]. Endothelin, a peptide known to produce severe vasoconstriction thus can be a potential agent to mediate the capsaicin-induced hypertension. Thus, the involvement of endothelin cannot be excluded. International Journal of Cardiology xxx (2010) xxx–xxx ⁎ Corresponding author. Tel.: + 91 542 2369069; fax: + 91 542 2367568. E-mail address: desh48@yahoo.com (S.B. Deshpande). IJCA-12516; No of Pages 2 0167-5273/$ – see front matter © 2010 Published by Elsevier Ireland Ltd. doi:10.1016/j.ijcard.2010.02.034 Contents lists available at ScienceDirect International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard ARTICLE IN PRESS Please cite this article as: Dutta A, Deshpande SB, Mechanisms underlying the hypertensive response induced by capsaicin, Int J Cardiol (2010), doi:10.1016/j.ijcard.2010.02.034