Ruthenium‐red inhibits CGRP release by capsaicin and resiniferatoxin but not by ouabain, bradykinin or nicotine in guinea‐pig heart: correlation with effects on cardiac contractility

Abstract

1 The possible influence of ruthenium-red (RR) on contractility and outflow of calcitonin gene-related peptide (CGRP)-like and neuropeptide Y (NPY)-like immunoreactivity (LI) from the heart of the guineapig induced by capsaicin, resiniferatoxin, nicotine, ouabain or bradykinin was studied in vitro. 2 In the isolated right atrium, exposure to capsaicin evoked an increase in contractile rate and tension simultaneously with an enhanced outflow of CGRP-LI, indicating release from the atria. Repeated administration of capsaicin induced tachyphylaxis. Incubation with RR markedly attenuated the capsaicinevoked release of CGRP-LI while no clear-cut effects were seen on contractile tension or rate. 3 In the isolated whole heart, perfusion with capsaicin induced an increased outflow of CGRP-LI and stimulated heart rate, while a negative inotropic effect was observed. A second administration of capsaicin to the same preparations failed to influence the CGRP-LI outflow and in these experiments the positive chronotropic effect was absent while the negative inotropic action remained unchanged. Capsaicinperfusion in the presence of RR failed to induce any increased outflow of CGRP-LI from the hearts or changes in contractile activity. However, after 1 h of rinsing with Tyrode solution repeated capsaicin perfusion in the absence of RR caused a clear-cut (60% of control) release of CGRP-LI and contractile responses were restored.4 Perfusion with resiniferatoxin evoked a RR-sensitive, clear-cut increased CGRP-LI output without any effects on contractile force or heart rate. Repeated administration of resiniferatoxin induced tachyphylaxis with respect to outflow. Capsaicin perfusion after resiniferatoxin did not influence cardiac rate, force or CGRP-LI outflow suggesting development of cross-tachyphylaxis. 5 Perfusion with RR did not influence the outflow of CGRP-LI or contractility changes evoked by perfusion with nicotine, ouabain or bradykinin. In addition, the release of NPY-LI by nicotine remained unchanged in the presence of RR. Furthermore, the positive chronotropic effect of human CGRP alpha remained intact in the presence of RR. 6 It is concluded that RR selectively inhibits capsaicin-and resiniferatoxin-induced excitation of cardiac sensory nerves as revealed by inhibition of both CGRP-LI release and the cardiostimulatory action of capsaicin. RR also seems to protect the cardiac capsaicin-sensitive fibres from the development of tachyphylaxis to capsaicin. Finally, RR prevents the capsaicin-evoked negative inotropic effect which is not related to activation of sensory nerves.

A role for sensory nerves in the late asthmatic response

“…Further evidence for a neuronal component to the LAR was the marked blockade observed after administration of the non-specific cation channel blocker ruthenium red in both species 25 26. This finding supports the hypothesis that OVA challenge can activate sensory nerves resulting in a central neural reflex and ultimately smooth muscle contraction.…”

Effects of Oral Nicotine on Rat Liver Stereology

“…The actions of the nicotine have been extensively investigated in humans, animals and a variety of cellular systems (West et al, 2003;Bao et al, 2005;Chu et al, 2005;Fang & Svoboda, 2005;Benowitz et al, 2006;Ochiai et al;Ueno et al, 2006;Wang et al, 2006). Predominant nicotine effects consist of: increase in heart rate and cardiac contractility (Franco-Cereceda et al, 1991;Benowitz et al, 2002;Pausova et al, 2003), increase in the blood pressure (Pausova et al; Ochiai et al), reduction of temperature skin (Plowchalk et al;Russell et al, 2004) and mobilization of the sugar in the blood (Gilbert et al, 2000). Reports about In vitro results shown: increase in the hormones synthesis and release (Seaman et al, 1977;Damaj, 2001;Wessler et al, 2003), activation of ERK (Chen et al, 1994;Szajerka & Kwiatkowska, 1997) and transcription nuclear factors (inflammatory factors as NFkB and AP-1) (Pennypacker et al; Pandey et al; Ueno et al), production of shock proteins Fig.…”

Potentiation of evoked calcitonin gene‐related peptide release from oral mucosa: a potential basis for the pro‐inflammatory effects of nicotine

“…Nicotine or other nicotinic agonists applied to sensory neurons has been shown to activate these neurons both in vitro (Steen & Reeh, 1993; Liu & Simon, 1993) and in vivo (Tanelian, 1991). Nicotine is known to directly stimulate the release of immunoreactive CGRP (iCGRP) in several tissues including heart (Franco‐Cereceda et al. , 1991, 1992), trachea (Hua et al.…”