Guinea pig pulmonary mechanics: altered sensitivity to carbachol by cadmium and/or selenium.
Male Hartley guinea pigs (480-610 g) were treated intratracheally as follows: saline, cadmium (Cd, 0.3 mg), selenium (Se, 0.3 or 0.06 mg), or Se (0.06 mg) and Cd (0.3 mg) simultaneously. Selenium and Cd were administered as sodium selenite and cadmium chloride, respectively. Twenty-four h later, dynamic lung compliance (Cdyn) and pulmonary resistance (Rp) were measured before (baseline Cdyn and Rp) and after carbachol administration (0.0001, 0.001, 0.01, and 0.1 mumol/kg, intravenously). Results indicated a significant decrease in baseline Cdyn caused by 0.3 mg of Cd, 0.3 mg or 0.06 mg of Se, and 0.3 mg of Cd with 0.06 mg of Se (p < 0.05). A significant increase in baseline Rp due to 0.3 mg of Se was observed (p < 0.05). Carbachol decreased Cdyn significantly below baseline, evident after lower doses of carbachol, in guinea pigs pretreated with 0.3 mg of Se, whereas a significant improvement in Cdyn was seen after 0.0001 mumol/kg carbachol in the group pretreated with Se and Cd simultaneously (p < 0.05) compared with the respective baseline values of the saline-treated group. Similarly, a significant increase in Rp was observed after carbachol in groups pretreated with 0.3 mg of Cd or Se (p < 0.05). Results also indicated a significant increase in large airway constriction caused by Cd and/or Se (p < 0.05). A leftward shift in the carbachol dose-response curve indicated increased sensitivity to carbachol in Cd- and/or Sepretreated guinea pigs.
Bell
R R
RR
Novartis Pharmaceuticals Corporation, Summit, New Jersey 07901-1398, USA.
Soliman
M R
MR
Nonavinakere
V K
VK
Hammerbeck
D M
DM
Early
J L
JL
D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects; D019256:Cadmium Chloride / Q000008:administration & dosage / Q000633:toxicity*; D002217:Carbachol / Q000494:pharmacology*; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004338:Drug Combinations; D006168:Guinea Pigs; D008171:Lung Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology*; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology*; D018038:Sodium Selenite / Q000008:administration & dosage / Q000633:toxicity*
D002273:Carcinogens; D004338:Drug Combinations; D018721:Muscarinic Agonists; D002217:Carbachol; D018038:Sodium Selenite; D019256:Cadmium Chloride