Inhibition of vascular smooth muscle cell growth by angiotensin type 2 receptor stimulation for in vitro organ culture model.
Recent data suggest that AT2 receptors in smooth muscle cells (VSMCs) of adult vessels may counterbalance AT1 receptor activity by inhibiting cell growth. The role of AT2 receptors in VSMC proliferation was investigated by using an in vitro organ culture model in which the sprouting of tubular structures was assessed. In preparations with endothelium, tubular growth was unaffected by angiotensin II (Ang II) but was inhibited by 50 +/- 9% by losartan and was increased by 110 +/- 15% by the AT2 antagonist PD123177. In endothelium-deprived preparations, growth inhibition (-49.1 +/- 0.5%) was observed when angiotensin II was added together with losartan 1 microM, whereas stimulation (59.8 +/- 14%) was induced by angiotensin II with 1 microM PD123177. In cultured VSMCs angiotensin II slightly promoted growth that was inhibited by losartan but was unaffected by PD123177. AT1a, AT1b, and AT2 mRNA expression was demonstrated in cells isolated from tubular structures grown from intact and endothelium-deprived rings, but only AT1a and AT1b mRNA was detected in cultured VSMCs. In conclusion, this paper proposes an in vitro organ culture model in which the expression of AT2 receptors in VSMCs is preserved and demonstrates AT2 receptor-mediated inhibition of VSMC proliferation in adult vessels.
Brogelli
Laura
L
Laboratory of Cardiovascular and Microvascular Pharmacology, Department of Preclinical and Clinical Pharmacology, University of Florence, Italy.
Parenti
Astrid
A
Ledda
Fabrizio
F
D020533:Angiogenesis Inhibitors / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D000804:Angiotensin II / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D009924:Organ Culture Techniques / Q000295:instrumentation / Q000379:methods; D051381:Rats; D011945:Receptors, Angiotensin / Q000819:agonists / Q000378:metabolism / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D020533:Angiogenesis Inhibitors; D057911:Angiotensin Receptor Antagonists; D011945:Receptors, Angiotensin; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D019808:Losartan