Altered mitogen-activated protein kinase activation in vascular smooth muscle cells from spontaneously hypertensive rats.
1. We previously reported that activation function of mitogen-activated protein kinases (MAPK) is enhanced in aorta strips from both prehypertensive and hypertensive spontaneously hypertensive rats (SHR) and that this enhancement of MAPK activation results from enhanced MAPK activation reactivity to angiotensin (Ang) II in SHR aorta strips. 2. The purpose of the present study was to examine whether the enhanced function of the vascular angiotensin system observed in SHR aorta strips results from genetic alterations of vascular smooth muscle cells from SHR. 3. Basal MAPK activity was within normal limits in cells from 4-week-old SHR, whereas enzyme activity was enhanced in 9-week-old SHR compared with age-matched Wistar-Kyoto (WKY) rats. 4. Mitogen-activated protein kinase activation reactivity to AngII and endothelin-1 was enhanced in 9-week-old SHR cells but not in 4-week-old SHR cells. The enhancement of basal MAPK activity in 9-week-old SHR cells was abolished by a combination of the angiotensin AT(1) receptor antagonist losartan and the endothelin receptor antagonist BQ123. 5. These findings suggest that MAPK activation function in 4-week-old SHR cells is not enhanced. Thus, it appears that factors outside vascular smooth muscle cells are needed for the enhanced MAPK activation observed in 4-week-old SHR aorta strips. In 9-week-old SHR, MAPK activation function is enhanced in cells themselves and this function may, at least in part, contribute to the enhanced MAPK activation observed in SHR aorta strips.
Kubo
Takao
T
Department of Pharmacology, Showa Pharmaceutical University, Machida, Tokyo, Japan. kubo@ac.shoyaku.ac.jp
Ibusuki
Takahiro
T
Chiba
Satoshi
S
Kambe
Toshie
T
Fukumori
Ryuji
R
D000375:Aging / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic / Q000201:enzymology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020022:Genetic Predisposition to Disease; D006973:Hypertension / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000201:enzymology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D004791:Enzyme Inhibitors; D010456:Peptides, Cyclic; D020928:Mitogen-Activated Protein Kinases; D019808:Losartan; C072247:cyclo(Trp-Asp-Pro-Val-Leu)