Receptor-mediated effects of angiotensin II on growth of vascular smooth muscle cells from spontaneously hypertensive rats.
This study examines the effects of angiotensin II on hypertrophy and proliferation of aortic smooth muscle cells from spontaneously hypertensive and Wistar-Kyoto rats and the receptor subtypes mediating these effects. In quiescent confluent cells, angiotensin II induced a dose-dependent increase in thymidine and leucine incorporation without stimulating cell proliferation. In nonconfluent cells, angiotensin II stimulated cell proliferation only in combination with a submaximal concentration of fetal calf serum. These effects were enhanced in cells from spontaneously hypertensive rats compared with Wistar-Kyoto rats. The effects of angiotensin II could be blocked by the AT1 receptor antagonist DuP 753 but not by the AT2 receptor ligand PD 123177. In receptor binding studies with cells derived from both rat strains, AT1-typical binding was observed. These data show that the angiotensin II receptors present in vascular smooth muscle cells in culture from both rat strains are of the AT1 receptor subtype. This receptor subtype appears to mediate vascular smooth muscle cell hypertrophy and proliferation as well as vasoconstriction. Although no difference in the receptor profile was detectable between the two rat strains, the affinity for the ligands to the receptor and the receptor density tended to be greater in cells from spontaneously hypertensive rats than in cells from Wistar-Kyoto rats. These results may partly explain the greater hypotensive response to angiotensin II receptor blockade in spontaneously hypertensive rats than in Wistar-Kyoto rats, although both rat strains have the same plasma concentrations of angiotensin II.
Bunkenburg
B
B
Department of Cardiovascular Research, CIBA-GEIGY Ltd., Basel, Switzerland.
van Amelsvoort
T
T
Rogg
H
H
Wood
J M
JM
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D006973:Hypertension / Q000503:physiopathology*; D008024:Ligands; D008297:Male; D009124:Muscle Proteins / Q000096:biosynthesis; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D011869:Radioligand Assay; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011945:Receptors, Angiotensin / Q000502:physiology*
D008024:Ligands; D009124:Muscle Proteins; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D004247:DNA