Alterations in prostaglandin production in spontaneously hypertensive rat smooth muscle cells.
We have characterized angiotensin binding sites in cultured smooth muscle cells obtained from the aorta of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. In both strains of rats the binding of 125I-angiotensin II (125I-Ang II) in smooth muscle cells was time dependent and reached a maximum at 60 minutes. Scatchard analysis revealed a single binding site in both strains with equilibrium constants (KD) of 5.35 nmol/L in SHR and 3.47 nmol/L in WKY rats. Binding capacities (Bmax) in smooth muscle cells averaged 270 and 150 fmol/mg protein in SHR and WKY rats, respectively. Angiotensin peptides competed for 125I-Ang II binding with an order of potency of Ang II > angiotensin-(1-7) = angiotensin I. In smooth muscle cells of the SHR, basal prostaglandin E2 (PGE2) and prostacyclin (prostaglandin I2 [PGI2]) release were threefold and 15-fold lower than that found in WKY rat smooth muscle cells. Ang II as well as angiotensin-(1-7) stimulated PGE2 and PGI2 release in WKY rat smooth muscle cells. In smooth muscle cells from SHR, Ang II increased the production of both PGE2 and PGI2, whereas angiotensin-(1-7) enhanced only PGE2 but not PGI2 release. There was no significant difference between Ang II-stimulated PGE2 and PGI2 release or angiotensin-(1-7)-stimulated PGE2 production in SHR and WKY rat smooth muscle cells. However, angiotensin-(1-7)-stimulated PGI2 release was significantly lower (p < 0.0005) in SHR compared with WKY smooth muscle cells. Collectively, the data suggest that smooth muscle cells of SHR contain a higher number of angiotensin binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Brain and Vascular Research, Cleveland Clinic Foundation, Ohio.
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N
Jaiswal
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RK
Jaiswal
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Tallant
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Diz
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Ferrario
D000803:Angiotensin I; D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis*; D011464:Epoprostenol / Q000096:biosynthesis*; D006973:Hypertension / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011945:Receptors, Angiotensin / Q000378:metabolism
D010446:Peptide Fragments; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D000803:Angiotensin I; D011464:Epoprostenol; C118790:angiotensin I (1-7); D015232:Dinoprostone