NSAID Anti Inflammatory Essay

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Bioscience Hypotheses (2009) 2, 290e294 available at www.sciencedirect.com

journal homepage: www.elsevier.com/locate/bihy

NSAID-induced gut inflammation and vasoconstriction: Causes and potential reversal with beta-CGRP e A hypothesis*
Chandra Somasundaram a,b, Rahul K. Nath a,b, Joseph Perkinson c,
Siva G. Somasundaram d,e,*, Ingvar Bjarnason f a Intron Pharmaceuticals, Houston, TX 77005, USA
Texas Nerve and Paralysis Institute, Houston, TX 77030, USA c Hospital drive, Victoria, TX 77901, USA d Department of Biology, School of Arts & Sciences, University of Houston-Victoria, TX 77479, USA e VFIC, Texas A&M University, College Station, TX 77845, USA f Department of Medicine, Guy’s, King’s, St Thomas’ Medical School, King’s College Hospital, Denmark Hill,
London SE5 9RS, UK b Received 1 April 2009; received in revised form 14 May 2009; accepted 22 May 2009

KEYWORDS
Calcitonin gene-related peptide (CGRP);
Inflammation;
Vasoconstriction;
Non-steroidal
anti-inflammatory drugs
(NSAIDs);
Cyclooxygenase-1
(COX-1);
Cyclooxygenase-2
(COX-2) inhibitor

Abstract Traditional non-steroidal anti-inflammatory drugs, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) inhibitors control inflammation. While these drugs are formulated to reduce one of the cardinal signs of inflammation by reducing prostaglandin levels at the site of inflammation, COX-1 inhibitors induce inflammation in the stomach as well as the small bowel. The COX-2 inhibitors, a large portion of the non-steroidal anti-inflammatory drug market, provide a gastro-intestinally safer class of drugs. However, COX-2 inhibitors induce vasoconstriction via actions in renal and cardiovascular tissues. Since COX-2 inhibitors also have anticancer potential, it is worthwhile to design drug formulations that will not cause hypertension or cardiovascular damage. An attempt has thus been made in this article to formulate a hypothesis to circumvent the COX inhibitors induced inflammation and vasoconstriction through COX independent activation of calcitonin gene-related peptide (CGRP), a potent vasodilator neuropeptide found throughout the vascular and sensory nervous system.
Published by Elsevier Ltd.

*
Sources of support: We greatly acknowledge the financial support from University of Houston-Victoria and USDA e CSREES # 2006-3440217121.
* Corresponding author. Tel.: þ1 281 275 8808; fax: þ1 281 275 3361.
E-mail address: somasundarams@uhv.edu (S.G. Somasundaram).

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