Stimulation of vascular glycosaminoglycan synthesis by subpressor angiotensin II in rats.
The vascular trophic effects of angiotensin II (Ang II) in small doses may precede its hypertension-producing effect, and de novo synthesis of components of extracellular matrix may be a requirement for Ang II-stimulated growth. In the present study, therefore, the incorporation of 35SO4 into glycosaminoglycans (synthesis) of aorta and bladder wall of young adult, male Sprague-Dawley rats was measured ex vivo after 48 hours of Ang II administration at two dose levels, 100 and 200 ng.kg-1.min-1 IP. Vehicle-infused rats served as controls. Compared with controls, systolic blood pressure was unchanged in rats receiving 100 ng.kg-1.min-1 Ang II and rose by 13 mm Hg (P < .05) in rats receiving the 200-ng.kg-1.min-1 dose. In Ang II-treated rats, glycosaminoglycan synthesis of the aorta was increased by 20% (P < .05) and 52% (P < .005) at the two dose levels, respectively. Glycosaminoglycan synthesis of bladder smooth muscle was also increased in Ang II-treated rats (P < .01), but the response was not dose dependent. By 7 to 10 days of Ang II administration (200 ng.kg-1.min-1), glycosaminoglycan synthesis of aorta returned toward baseline (P < .10, > .05). The rate of synthesis of subtypes of glycosaminoglycans in the aorta was proportionately increased by Ang II. The early occurrence, magnitude, and arterial pressure independence of Ang II-induced glycosaminoglycan synthesis suggest that restructuring of extracellular matrix may play an important role in both the trophic and hypertension-producing action of Ang II.
Simon
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Department of Medicine, VA Medical Center, Minneapolis, MN 55417.
Abraham
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Altman
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D000595:Amino Acid Sequence; D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D002809:Chondroitin Sulfates / Q000096:biosynthesis; D003871:Dermatan Sulfate / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D006025:Glycosaminoglycans / Q000096:biosynthesis*; D006497:Heparan Sulfate / Q000096:biosynthesis; D007700:Kinetics; D008297:Male; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013431:Sulfates / Q000378:metabolism; D013462:Sulfur Radioisotopes; D013997:Time Factors; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism*
D000804:Angiotensin II; D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D006025:Glycosaminoglycans; D006497:Heparan Sulfate; D013431:Sulfates; D013462:Sulfur Radioisotopes