Angiotensin and thromboxane in genetically hypertensive rats: renal blood flow and receptor studies.
The objective of this study was to test whether angiotensin II (ANG II) and thromboxane A2 (TxA2) contribute to the increased renal vascular reactivity observed in genetic hypertension. Under control conditions, ANG II reduced renal blood flow 35% more in spontaneously hypertensive (SHR) than in Wistar-Kyoto (WKY) rats. This strain difference was abolished by inhibition of prostaglandin synthesis with indomethacin and thus may be due to a deficiency in the action of endogenous vasodilator prostaglandins. The stable TxA2-receptor agonist U 46619 produced equal reductions of renal blood flow in SHR and WKY under control conditions. However, after indomethacin, the agonist-induced vasoconstriction was 70% more in SHR than in WKY, suggesting that SHR kidneys have an increased vascular reactivity to TxA2, which is unmasked when indomethacin reduces elevated levels of endogenous TxA2. Radiolabeled ligand binding studies for ANG II and TxA2 were undertaken in glomeruli isolated from WKY and SHR at 6 and 12 wk of age. Scatchard analysis revealed a single high-affinity receptor site for ANG [dissociation constant (Kd) = 1.2 nM], which was similar in both strains and ages of rats. All groups also showed a single high-affinity TxA2 receptor site (Kd = 3.5 nM). No differences were observed in the ANG II receptor number between age-matched rats, although the density increased with age. The density of TxA2 receptors was threefold higher in young SHR and nearly twofold higher in 12-wk-old SHR than in age-matched WKY controls. These findings indicate that the exaggerated renal vascular reactivity of SHR to ANG II and TxA2 may be mediated by a shift in the balance between endogenous vasoactive prostanoids and increased density of renal TxA2 receptors.
Chatziantoniou
C
C
Department of Physiology, University of North Carolina, Chapel Hill 27599.
Arendshorst
W J
WJ
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D006973:Hypertension / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D007668:Kidney / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011945:Receptors, Angiotensin / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000378:metabolism; D017482:Receptors, Thromboxane; D012079:Renal Circulation / Q000187:drug effects*; D013928:Thromboxane A2 / Q000494:pharmacology*
D011945:Receptors, Angiotensin; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D000804:Angiotensin II; D013928:Thromboxane A2