Spontaneously hypertensive rat vascular smooth muscle cells in culture exhibit increased growth and Na+/H+ exchange

Journal Article · Wed Mar 01 04:00:00 EST 1989 · J. Clin. Invest.; (United States)

DOI:https://doi.org/10.1172/JCI113964· OSTI ID:6172194

Berk, B C; Vallega, G; Muslin, A J; Gordon, H M; Canessa, M; Alexander, R W

The cellular mechanisms responsible for abnormalities in spontaneously hypertensive rat (SHR) vascular smooth muscle cell (VSMC) growth and vasoreactivity are not defined. Because Na+/H+ exchange, which we have previously demonstrated in cultured VSMC, plays an essential role in mediating growth factor responses, we hypothesized that abnormalities in SHR growth regulation might be reflected in the activity of this transporter. To test this hypothesis, we studied DNA synthesis and Na+/H+ exchange (measured as the rate of amiloride-sensitive intracellular alkalinization or Na+ influx) in early subcultures (less than 6) of aortic VSMC from 12-wk-old SHR and Wistar Kyoto (WKY) animals. Serum-deprived SHR VSMC grew more rapidly in response to 10% serum with an increase in (3H)thymidine incorporation of 439% compared with 191% in WKY controls. Basal intracellular pH (pHi) values determined by fluorescent pH measurements were 7.37 +/- 0.04 and 7.27 +/- 0.03 (P less than 0.05) in early passage SHR and WKY, respectively. Acid recovery (initial pHi = 6.8) by SHR VSMC was faster than by WKY VSMC as measured by alkalinization or by amiloride-sensitive 22Na+ influx. In comparison to WKY cells early passage SHR VSMC exhibited 2.5-fold greater alkalinization and amiloride-sensitive 22Na+ influx in response to 100 nM angiotensin II. During serial passage, WKY cells acquired enhanced Na+/H+ exchange and growth rates so that by passage 6, these differences were no longer present. These findings in early cultures of SHR VSMC, removed from the in vivo neurohumoral milieu, suggest that increased Na+/H+ exchange in SHR may reflect alterations in Na+ homeostasis that might contribute to altered SHR VSMC function such as enhanced growth and vasoreactivity.

• Research Organization: Brigham and Women's Hospital, Boston, MA (USA)
• OSTI ID: 6172194
• Journal Information: J. Clin. Invest.; (United States), Journal Name: J. Clin. Invest.; (United States) Vol. 83:3; ISSN JCINA
• Country of Publication: United States
• Language: English

Related Subjects

550901* -- Pathology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKALI METAL COMPOUNDS
ALKALI METAL ISOTOPES
ANGIOTENSIN
ANIMAL CELLS
ANIMALS
AZINES
BARYONS
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BIOLOGICAL VARIABILITY
CARDIOVASCULAR AGENTS
CARDIOVASCULAR DISEASES
CELL CULTURES
CELL PROLIFERATION
DISEASES
DNA
DNA REPLICATION
DRUGS
ELEMENTARY PARTICLES
FERMIONS
GENETIC VARIABILITY
GLOBULINS
GROWTH FACTORS
HADRONS
HETEROCYCLIC COMPOUNDS
HOMEOSTASIS
HYPERTENSION
ION EXCHANGE
ISOTOPE APPLICATIONS
ISOTOPES
LABELLED COMPOUNDS
LIGHT NUCLEI
MAMMALS
MEMBRANE TRANSPORT
MITOGENS
MUSCLES
NUCLEI
NUCLEIC ACID REPLICATION
NUCLEIC ACIDS
NUCLEONS
NUCLEOSIDES
NUCLEOTIDES
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PATHOGENESIS
PROTEINS
PROTONS
PYRIMIDINES
RADIOISOTOPES
RATS
RIBOSIDES
RODENTS
SODIUM 22
SODIUM COMPOUNDS
SODIUM ISOTOPES
SYMPTOMS
THYMIDINE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VASCULAR DISEASES
VASOCONSTRICTORS
VERTEBRATES
YEARS LIVING RADIOISOTOPES