Nitroglycerin protects small intestine from ischemia-reperfusion injury via NO-cGMP pathway and upregulation of alpha-CGRP.
BACKGROUND
Nitroglycerin (NTG) has been reported to possess preconditioning-like (PCL) protections on heart and other tissues. Our previous studies showed that NTG has acute PCL effects on rat small intestine. The present studies were designed to study whether NTG has delayed PCL protection on rat small intestine and to explore its mechanism(s).


METHODS
The intestine lesions were evaluated by histologic examination and serum lactate dehydrogenase (LDH) measurement. The effects of nitric oxide (NO), cGMP, and alpha-calcitonin gene-related peptide (CGRP) synthesis on the effects of NTG were analyzed.


RESULTS
Pretreatment with NTG (0.12 mg/kg i.v.) 24 h before ischemia-reperfusion (I/R) of super mesenteric artery significantly reduced histologic lesions and serum LDH with elevated blood levels of NO and CGRP. Inhibition of guanylate cyclase by methylene blue (30 mg/kg i.p.) or specific depletion of transmitters in capsaicin-sensitive sensory nerve by capsaicin (50 mg/kg s.c.) abrogated the protection conferred by NTG. Reverse-transcription polymerase chain reaction analysis showed that NTG upregulates the expression of alpha-CGRP messenger RNA (mRNA), but not beta-CGRP mRNA in lumbar dorsal root ganglia.


CONCLUSIONS
In conclusion, NTG prevents rat small intestine from I/R injury by delayed PCL effects 24 h after administration. The protective effects are mediated by NO-cGMP pathway and alpha-CGRP upregulation.
Li
Jie
J
Department of Pharmacology, Shanxi Medical University, Xinjian South Road 56, Taiyuan, Shanxi Province 030001, People's Republic of China.
Zhang
Mingsheng
M
Yang
Caihong
C
Dun
Ying
Y
Zhang
Yi
Y
Hao
Yibin
Y
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology; D006152:Cyclic GMP / Q000502:physiology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019194:Ischemic Preconditioning / Q000379:methods; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D005996:Nitroglycerin / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D014665:Vasodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use
D014665:Vasodilator Agents; D009569:Nitric Oxide; D006162:Guanylate Cyclase; D005996:Nitroglycerin; D006152:Cyclic GMP; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin