The role of angiotensin II in vascular smooth muscle cell growth.
One of the major consequences of hypertension is an increase in the thickness of the arterial medial smooth muscle cell layer. This has been shown in both large and medium size resistance vessels caused by smooth muscle cell hypertrophy. Both in vivo and in vitro data suggest that the vasoconstrictor peptide angiotensin II (Ang II) may play an important role in the development of the smooth muscle hypertrophy. We have demonstrated that Ang II, when added to quiescence cultures of vascular smooth muscle cells, results in the rapid induction of the early growth response genes c-fos, c-myc, and c-jun. This is due to new transcription as demonstrated by nuclear runoff transcription assay, but is not dependent on new protein synthesis, as it is not blocked by the addition of cycloheximide. The effect is due, however, to an increase in intracellular calcium, suggesting that any vasoconstrictor which results in an increase in intracellular calcium may act in this manner. Following the induction of the early growth response genes there is delayed induction of the platelet derived growth factor A-chain gene. Data from our laboratory and from that of others has shown in preliminary studies that blockade of either the Ang II-induced increases in c-fos or in the platelet-derived growth factor A-chain increases smooth muscle cell protein synthesis. This suggests that Ang II and other vasoconstrictors may play an important role in vascular smooth muscle growth, in hypertension and also in atherosclerosis and following balloon injury of the arterial wall.(ABSTRACT TRUNCATED AT 250 WORDS)
Naftilan
A J
AJ
University of Alabama, Birmingham.
D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000473:pathology*; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000473:pathology
D000804:Angiotensin II