Vascular smooth muscle growth in genetic hypertension: evidence for multiple abnormalities in growth regulatory pathways.
OBJECTIVE
To gain insight into the mechanisms which contribute to the development of vascular hypertrophy in the spontaneously hypertensive rat (SHR).


METHODS
These experiments were performed under conditions which most closely mimic the growth of smooth muscle in blood vessels, i.e. once cell-cell contact has been achieved.


METHODS
A comparison of the growth characteristics (growth rates and cell density at quiescence) of vascular smooth muscle cells (VSMC) from SHR and normotensive Wistar-Kyoto (WKY) rats.


RESULTS
In the presence of foetal calf serum (1, 2.5, 5 and 10%), early passaged VSMC from SHR exhibited higher growth rates and reached higher densities at quiescence than VSMC from WKY rats. Accelerated growth rates could not be attributed to differences in cell-cell interactions. Also, growth rates and cell density at quiescence appear to be regulated by distinct mechanisms. Transforming growth factor-beta 1 (TGF-beta 1) caused an inhibition of serum-stimulated proliferation of confluent VSMC from WKY rats. In contrast, TGF-beta 1 had little, if any, inhibitory action upon the growth of VSMC from SHR. Scatchard analysis of 125I-TGF-beta 1 binding to VSMC from both strains yielded a single class of high affinity binding sites.


CONCLUSIONS
VSMC from SHR exhibit enhanced proliferation, attain a higher cell density at quiescence and are less susceptible to growth inhibition by TGF-beta 1 than VSMC from WKY rats. All these characteristics of SHR VSMC may contribute to the development of vascular hypertrophy in this strain.
Saltis
J
J
Baker Medical Research Institute, Alfred Hospital, Prahran, Victoria, Australia.
Bobik
A
A
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D002452:Cell Count; D002478:Cells, Cultured; D003470:Culture Media; D006973:Hypertension / Q000235:genetics*; D008297:Male; D024510:Muscle Development; D009131:Muscle, Smooth, Vascular / Q000254:growth & development*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D016212:Transforming Growth Factor beta / Q000502:physiology
D003470:Culture Media; D016212:Transforming Growth Factor beta