Effects of long-term laxative treatment on rat mesenteric resistance vessel responses in vitro.
The effects of long-term treatment with the laxatives senna and 1,8-dihydroxyanthraquinone (danthron) were investigated in isolated mesenteric vascular beds of rats. The senna was administrated as ground senna pods mixed with milk chocolate. Danthron was also administered in this way. Chocolate-fed, senna-fed, and danthron-fed rats were supplied with usual feed, supplemented with chocolate, chocolate adulterated with ground senna pods, and chocolate adulterated with danthron, respectively. A group of control rats had no supplement. Perivascular nerve stimulation elicited frequency-dependent vasoconstriction of the mesenteric bed. There were no significant differences in responsiveness to perivascular nerve stimulation among mesenteric beds from the four groups. During two separate consecutive applications of capsaicin, a sensory neurotoxin, pressor responses to nerve stimulation of vascular beds from the control and chocolate-fed rats were inhibited on both occasions. However, in mesenteric beds from the senna-fed and danthron-fed groups, inhibition of pressor responses was the same on the first application of capsaicin as in the control and chocolate-fed groups, but the effect of the second application of capsaicin was greatly reduced. Calcitonin gene-related peptide, adenosine 5'-triphosphate, and adenosine mimicked the inhibitory action of capsaicin on nerve stimulation in all groups, while substance P was without effect. There was no significant difference in responsiveness to these agents among the four groups. These results suggest that senna or its metabolites may cause a sensory neuropathy of mesenteric resistance vessels and that calcitonin gene-related peptide, adenosine 5'-triphosphate, and adenosine, but not substance P, are possible candidates as mediators of the inhibitory effects induced by capsaicin.
Ralevic
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V
Department of Anatomy and Developmental Biology, University College London, England.
Hoyle
C H
CH
Burnstock
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G
D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D002400:Cathartics / Q000494:pharmacology*; D004558:Electric Stimulation; D005260:Female; D008638:Mesenteric Arteries / Q000294:innervation; D051381:Rats; D011919:Rats, Inbred Strains; D012676:Senna Extract / Q000494:pharmacology*; D013152:Splanchnic Circulation / Q000187:drug effects*; D013373:Substance P / Q000494:pharmacology; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects
D000880:Anthraquinones; D002400:Cathartics; D013373:Substance P; D012676:Senna Extract; D000255:Adenosine Triphosphate; D015740:Calcitonin Gene-Related Peptide; D000241:Adenosine; D002211:Capsaicin; C004315:danthron