title: Attenuation of L-type Ca²⁺ channel expression and vasomotor response in the aorta with age in both Wistar-Kyoto and spontaneously hypertensive rats.
abstract: Age-related vascular diseases are induced by vascular dysfunction, which involves changes in the vasomotor response. The voltage-dependent L-type calcium channel (VDCC) protein is involved in the regulation of vessel function (contraction/relaxation action). In the present study, we evaluated age-related vasomotor function and expression of the signal-related target proteins, including VDCC, using thoracic aorta from both 8- and 40-week old Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). In contraction experiments using aortic rings, vasomotor responses of both phenylephrine-induced contraction and acetylcholine-induced relaxation were significantly attenuated with age in SHR, whereas WKY did not lose activity with age. Contraction induced by angiotensin II was impaired only for the 40-week old SHR among all the rat groups tested, although enhanced AT1R/reduced AT2R expression with age was observed for both WKY and SHR. In contrast, a vasomotor responsiveness to Bay K 8644 (a VDCC agonist) at the initial contraction phase was significantly attenuated in both 40-week WKY and SHR with significant reduction of VDCC protein expression. The reduced VDCC expression in 40-week old rats significantly lowered the relaxation activity of VDCC blockers, such as verapamil and Trp-His, but did not affect that of nifedipine. Taken together, we provided the first evidence that aging caused a reduction of VDCC expression in rat aorta, irrespective of the rat strain, along with diminishment of the therapeutic potential of VDCC blockers.
authors.affiliation: The Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School of Kyushu University, Hakozaki, Higashi-ku, Fukuoka, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Fukuda
authors.affiliation: The Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School of Kyushu University, Hakozaki, Higashi-ku, Fukuoka, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kuroda
authors.affiliation: The Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School of Kyushu University, Hakozaki, Higashi-ku, Fukuoka, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Kono
authors.affiliation: The Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School of Kyushu University, Hakozaki, Higashi-ku, Fukuoka, Japan.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Miyamoto
authors.affiliation: The Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School of Kyushu University, Hakozaki, Higashi-ku, Fukuoka, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: The Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School of Kyushu University, Hakozaki, Higashi-ku, Fukuoka, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Matsui
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000375:Aging / Q000378:metabolism / Q000502:physiology*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D000804:Angiotensin II; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester