Increased susceptibility of rat gastric mucosa to ulcerogenic stimulation with aging. Role of capsaicin-sensitive sensory neurons.
We examined the influences of aging on gastric damage and gastric mucosal blood flow (GMBF) responses induced by acid back-diffusion, following the barrier disruption, and investigated the relation of capsaicin-sensitive sensory nerves to these changes. Male Fischer rats 3, 13, and 24 months old were used. Under urethane anesthesia, a rat stomach was mounted on a chamber, and gastric potential difference (PD), luminal H+ loss, and GMBF were measured before, during, and after exposure to 20 mM sodium taurocholate (TC) for 30 min, in the presence of 50 mM HCl. Mucosal exposure to TC caused surface cell damage, PD reduction, and acid back-diffusion (luminal H+ loss) in all groups of rats; delta PD reduction and the amount of H+ loss were not significantly different between young and aged rats. In young rats, a marked increase of GMBF was observed with luminal acid loss following TC treatment, yet it resulted in less damage in the gastric mucosa. In aged rats, however, such GMBF responses were apparently mitigated, leading to a significant worsening of gastric mucosal lesions induced by TC. Mucosal application of capsaicin (0.1 mg/ml) caused an increase of GMBF in young rats, but this response was significantly attenuated in aged rats. In addition, the amount of calcitonin gene-related peptide (CGRP) released in the isolated stomach in response to capsaicin (1 X 10(-5) M) was significantly lower in aged animals when compared to young rats. These findings suggest that the gastric mucosa of aged rats is more vulnerable to acid back-diffusion following the barrier disruption, partly because of dysfunction of GMBF responses mediated by capsaicin-sensitive sensory neurons in the acidic conditions.
Miyake
H
H
Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Japan.
Inaba
N
N
Kato
S
S
Takeuchi
K
K
D000375:Aging / Q000502:physiology*; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D002756:Cholagogues and Choleretics / Q000494:pharmacology; D005744:Gastric Acid / Q000502:physiology; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D011984:Sensory Receptor Cells / Q000187:drug effects*; D013276:Stomach Ulcer / Q000209:etiology* / Q000503:physiopathology; D013656:Taurocholic Acid / Q000494:pharmacology
D002756:Cholagogues and Choleretics; D013656:Taurocholic Acid; D002211:Capsaicin