Salt loading enhances rat renal TxA2/PGH2 receptor expression and TGF response to U-46,619.
The tubuloglomerular feedback (TGF) response is potentiated by thromboxane A2 (TxA2) and/or prostaglandin endoperoxide (PGH2) acting on specific receptors. Infusion of the TxA2/PGH2 mimetic, U-46,619, into conscious rats leads to hypertension that is potentiated by a high-salt intake. Therefore, we tested the hypothesis that a high-salt intake enhances the expression of transcripts for TxA2/PGH2 receptors in the kidney and glomeruli and enhances the response of TGF to TxA2/PGH2 receptor stimulation. Groups of rats were accommodated to a low-salt (LS), normal salt (NS), or high-salt (HS) diet for 8-10 days. TxA2/PGH2 receptor mRNA was detected by reverse transcription-polymerase chain reaction in kidney cortex, isolated glomeruli, and abdominal aorta. TxA2/PGH2 mRNA abundance was significantly (P < 0.001) increased during intake of high-salt compared with low-salt diets in the kidney cortex (1.34 +/- 0.10 vs. 0.84 +/- 0.04 arbitrary units) and isolated outer cortical glomeruli (0.68 +/- 0.04 vs. 0.32 +/- 0.03 arbitrary units), but there was no effect of salt on TxA2/PGH2 receptor mRNA expression in the aorta. Maximal TGF responses were assessed from the increase in proximal stop flow pressure (an index of glomerular capillary pressure) during increases in loop of Henle perfusion with artificial tubular fluid from 0 to 40 nl/min. Compared with vehicle, the enhancement of maximal TGF with U-46,619 (10(-6) M) added to the perfusate was greater in rats adapted to high-salt than normal salt (HS: +9.6 +/- 1.1 vs. NS: +5.1 +/- 0.4 mmHg; P < 0.001) or low-salt (LS: +3.8 +/- 1.3 mmHg; P < 0.001) intakes. Responses to U-46,619 at each level of salt intake were blocked by > 70% by the TxA2/PGH2 receptor antagonist ifetroban. In contrast, enhancement of TGF by peritubular capillary perfusion of arginine vasopressin (AVP; 10(-7) M) was similar in high-salt and low-salt rats (HS: +1.5 +/- 0.6 vs. LS: +1.6 +/- 0.5 mmHg; not significant). We conclude that salt loading increases selectively the abundance of TxA2/PGH2 receptor transcripts in the kidney cortex and glomerulus, relative to the aorta, and enhances selectively TGF responses to TxA2/PGH2 receptor activation but not to AVP.
Welch
W J
WJ
Division of Nephrology and Hypertension, Georgetown University Medical Center, Washington, District of Columbia 20007, USA.
Peng
B
B
Takeuchi
K
K
Abe
K
K
Wilcox
C S
CS
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology*; D000818:Animals; D001012:Aorta, Abdominal / Q000502:physiology; D005246:Feedback; D005786:Gene Expression Regulation / Q000187:drug effects*; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D007672:Kidney Cortex / Q000502:physiology; D007678:Kidney Glomerulus / Q000502:physiology; D008138:Loop of Henle / Q000502:physiology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011982:Receptors, Prostaglandin / Q000096:biosynthesis; D017482:Receptors, Thromboxane / Q000096:biosynthesis*; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D012016:Reference Values; D012982:Sodium, Dietary / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects*
D012333:RNA, Messenger; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D012982:Sodium, Dietary; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid