Altered signal transduction in vascular smooth muscle cells of spontaneously hypertensive rats.
The hypothesis that signal transduction mediated by platelet-derived growth factor (PDGF) and angiotensin II (Ang II) is altered in vascular smooth muscle (VSM) cells from the spontaneously hypertensive rat (SHR) was tested by measuring changes in the cytosolic free calcium concentration ([Ca2+]i). [Ca2+]i was measured in cultured aortic smooth muscle cells from SHRs and Wistar-Kyoto (WKY) normotensive rats using fura-2 as a calcium indicator and a microscopic digital image analysis system. Activation of cells with Ang II resulted in a prompt though transient rise in [Ca2+]i; the maximum increase was observed after 10-30-second intervals. On the other hand, activation of cells with PDGF BB produced an increase in [Ca2+]i with a 40-60-second lag period; the maximum increase was observed 2-4 minutes after the addition of PDGF. PDGF-stimulated increases in [Ca2+]i were markedly inhibited by the addition of the calcium channel antagonist verapamil (100 microM) as well as by removal of calcium from the extracellular bathing medium. However, Ang II-stimulated [Ca2+]i was not significantly affected by the addition of verapamil or by removal of extracellular calcium. These results would indicate that PDGF-mediated increases in [Ca2+]i in VSM cells are predominantly via Ca2+ influx, whereas Ang II-mediated increases are due to calcium release from intracellular pools. Basal and PDGF- and Ang II-stimulated increases in [Ca2+]i were significantly greater (p less than 0.05) in SHR VSM cells compared with WKY cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Bendhack
L M
LM
Department of Anatomy, University of Iowa College of Medicine, Iowa City 52242.
Sharma
R V
RV
Bhalla
R C
RC
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000032:analysis / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000166:cytology / Q000503:physiopathology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D015398:Signal Transduction / Q000502:physiology*
D015220:Calcium Channels; D010982:Platelet-Derived Growth Factor; D000804:Angiotensin II; D002118:Calcium