Response of aortic elastin synthesis and accumulation to developing hypertension and the inhibitory effect of colchicine on this response.
One of the well-known consequences of established hypertension is an increase in connective tissue proteins in the walls of the large arterial blood vessels. Using renal clip and Dahl salt-sensitive rat models of systemic hypertension, we investigated the effect of developing hypertension on elastin production and accumulation in rat aorta. In both models of hypertension, increased accumulation of arterial elastin appeared coincidentally with, and was proportional to, elevation of blood pressure. In spite of large increases in absolute amounts of elastin, the proportion of elastin present in the vessel wall remained essentially constant from the earliest stage of the response. These changes in elastin synthesis and accumulation took place in the absence of evidence of cell proliferation. Treatment of Dahl rats with colchicine during development of hypertension affected blood pressure rise only marginally but abolished the vascular hypertrophic response. Our results suggest that the response of elastin production to increased blood pressure is rapid and sensitive, and that the stimulus for increased synthesis is an increase in wall stress. The striking effect of colchicine may indicate a role of elements of the cytoskeleton in the perception of stress by the vascular smooth muscle cells or in the transduction of that stress into increased production of connective tissue proteins.
Keeley
F W
FW
Division of Cardiovascular Research, Hospital for Sick Children; Ontario, Canada.
Alatawi
A
A
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D003078:Colchicine / Q000494:pharmacology*; D004247:DNA / Q000032:analysis; D004549:Elastin / Q000096:biosynthesis*; D006973:Hypertension / Q000473:pathology / Q000503:physiopathology*; D006977:Hypertension, Renal / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013997:Time Factors
D004247:DNA; D004549:Elastin; D003078:Colchicine