Effect of capsaicin on plasma and tissue levels of insulin-like growth factor-I in spontaneously hypertensive rats.
OBJECTIVE
Plasma levels of insulin-like growth factor-I (IGF-I), an important substance for maintaining cardiovascular homeostasis, are lower in spontaneously hypertensive rats (SHR) than in normotensive Wistar Kyoto rats (WKY). Calcitonin gene-related peptide (CGRP) increases IGF-I production in vitro and in vivo, suggesting that stimulation of sensory neurons might increase the production of IGF-I in SHR.


METHODS
Levels of CGRP and IGF-I in plasma, kidneys and heart in WKY and SHR and cellular cyclic AMP levels in dorsal root ganglion neurons (DRGs) isolated from WKY and SHR were measured by an ELISA-based method.


RESULTS
Levels of CGRP and IGF-I in plasma, kidneys and heart of SHR were about half of those of WKY. Administration of capsaicin significantly increased levels of CGRP and IGF-I in plasma and tissues of SHR to the levels in WKY and these increases were completely reversed by pretreatment with capsazepine, an inhibitor of vanilloid receptor-1 activation. CGRP release and cellular levels of cAMP in DRGs isolated from SHR were significantly lower than those in DRGs isolated from WKY. Capsaicin increased both CGRP release and cellular cAMP levels in DRGs isolated from SHR to the levels in DRGs isolated from WKY.


CONCLUSIONS
Sensory neuron activation might be lower in SHR than in WKY probably due to decreased production of cAMP in sensory neurons, explaining why IGF-I levels in plasma and tissues are lower in SHR than in WKY.
Harada
Naoaki
N
Department of Translational Medical Science Research, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan.
Okajima
Kenji
K
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide / Q000097:blood; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D005727:Ganglia, Spinal / Q000187:drug effects; D006973:Hypertension / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000032:analysis* / Q000096:biosynthesis; D009475:Neurons, Afferent / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D000959:Antihypertensive Agents; D007334:Insulin-Like Growth Factor I; D000242:Cyclic AMP; D015740:Calcitonin Gene-Related Peptide; C071423:capsazepine; D002211:Capsaicin