title: The role of Na+/H+ exchange and growth factors in pulmonary artery smooth muscle cell proliferation.
abstract: Chronic hypoxia produces pulmonary hypertension, in part because of hypertrophy and hyperplasia of pulmonary artery smooth muscle cells (PA SMC). Platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) have been shown to stimulate SMC proliferation and may be involved in these vascular changes. Both factors cause a rise in intracellular pH (pHi) in systemic vascular SMC through stimulation of the Na+/H+ exchanger, an event that has been thought to be permissive, allowing cell proliferation in response to the growth factor. The present studies examined the possibility that the activation of Na+/H+ exchange is involved in the PA SMC mitogenic response to these growth factors. Na+/H+ exchange activity was assessed by monitoring pHi in cultured cells using the pH-sensitive dye, 2'7'-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF). PDGF (60 ng/ml) exposure led to a marked activation of Na+/H+ exchange, evidenced by a rise in pHi (mean +/- SEM) of 0.20 +/- 0.03 pH units (n = 5, P < 0.05). EGF (60 ng/ml) exposure produced a rise in pHi of 0.27 +/- 0.03 pH units (n = 5, P < 0.05). Dimethyl amiloride (DMA, 50 microM), a competitive inhibitor of Na+/H+ exchange, blocked the pH response to PDGF and EGF. PA SMC showed a proliferative response when exposed to PDGF and EGF which was attenuated by 50 microM DMA (n = 6). Thus, activation of the Na+/H+ exchanger may be important in pulmonary cell signaling in response to growth factors as it has been found to be in systemic vessels.
authors.affiliation: Massachusetts General Hospital, Pulmonary/Critical Care Unit, Boston 02114, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Quinn
authors.forename: C G
authors.initials: CG
authors.lastname: Dahlberg
authors.forename: J P
authors.initials: JP
authors.lastname: Bonventre
authors.forename: C R
authors.initials: CR
authors.lastname: Scheid
authors.forename: T
authors.initials: T
authors.lastname: Honeyman
authors.forename: P M
authors.initials: PM
authors.lastname: Joseph
authors.forename: B T
authors.initials: BT
authors.lastname: Thompson
authors.forename: C A
authors.initials: CA
authors.lastname: Hales
mesh_terms: D000468:Alkalies; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011651:Pulmonary Artery / Q000166:cytology; D017923:Sodium-Hydrogen Exchangers / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D000468:Alkalies; D010982:Platelet-Derived Growth Factor; D017923:Sodium-Hydrogen Exchangers; C039465:5-dimethylamiloride; D004815:Epidermal Growth Factor; D000584:Amiloride