Angiotensin II responses after protein kinase C activation in vascular smooth muscle cells of spontaneously hypertensive rats.
To examine the interaction of protein kinase C (PKC) with agonist-induced calcium fluxes in hypertension, cytosolic free calcium ([Ca2+]i) was measured in vascular smooth muscle cells (vSMC) of normotensive and spontaneously hypertensive rats (SHR) after incubation with phorbol,-12 myristate,-13 acetate (PMA) and application of angiotensin II (AII). To distinguish between calcium influx through voltage-dependent calcium channels and calcium mobilization from intracellular stores, the calcium agonist BayK 8644 was used. Resting [Ca2+]i was 108.0 +/- 10.6 nM (mean +/- SEM, n = 25) in normotensive and 102.0 +/- 11.4 nM (n = 21) in hypertensive cells. After pretreatment with PMA 10(-7) M for 60 min, resting [Ca2+]i of normotensive vSMC increased to 145.0 +/- 13.8 nM (n = 17) while the resting level of the hypertensive cells decreased to 68.0 +/- 2.4 nM (n = 14, p < 0.05 as compared with normotensive cells) in hypertensive vSMC. Maximum increase in [Ca2+]i induced with 10 M AII for normotensive and hypertensive vSMC was similar: 230.5 +/- 34.4 nM (n = 14) and 212.5 +/- 26.7 nM (n = 17). After pretreatment with PMA 10(-7) M, the maximum increase in [Ca2+]i induced by AII in hypertensive cells was limited to 108.0 +/- 6.2 nM (p < 0.05 as compared with normotensive cells), whereas the increase in [Ca2+]i in normotensive vSMC remained the same as before: 211.5 +/- 23.4 nM. After administration of 10(-5) M BayK 8644, [Ca2+]i increased by 54.3 +/- 12.2 nM (n = 4) and 43.4 +/- 17.4 nM (n = 5) in normotensive and hypertensive vSMC, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Neusser
M
M
Medinische Universitäts Poliklinik, University of Münster, Germany.
Tepel
M
M
Zidek
W
W
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000804:Angiotensin II / Q000097:blood*; D000818:Animals; D002478:Cells, Cultured; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation; D016257:Fura-2; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000201:enzymology*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000804:Angiotensin II; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D016257:Fura-2