Angiotensin II enhances connecting tubule glomerular feedback.
Increasing Na delivery to epithelial Na channels (ENaCs) in the connecting tubule (CNT) causes dilation of the afferent arteriole (Af-Art), a process we call CNT glomerular feedback (CTGF). Angiotensin II (Ang II) stimulates ENaC in the collecting duct via Ang II type 1 receptors. We hypothesized that Ang II in the CNT lumen enhances CTGF by activation of Ang II type 1 receptors, protein kinase C and ENaC. Rabbit afferent arterioles and their adherent CNT were microperfused and preconstricted with norepinephrine. Each experiment involved generating 2 consecutive concentration-response curves by increasing NaCl in the CNT lumen. During the control period, the maximum dilation of the afferent arteriole was 7.9±0.4 μm, and the concentration of NaCl in the CNT needed to achieve half maximal response (EC(50)) was 34.7±5.2 mmol/L. After adding Ang II (10(-9) mol/L) to the CNT lumen, the maximal response was 9.5±0.7 μm and the EC(50) was 11.6±1.3 mmol/L (P=0.01 versus control). Losartan, an Ang II type 1 antagonist (10(-6) mol/L) blocked the stimulatory effect of Ang II; PD123319, an Ang II type 2 antagonist (10(-6) mol/L), did not. The protein kinase C inhibitor staurosporine (10(-8) mol/L) added to the CNT inhibited the stimulatory effect of Ang II. The ENaC inhibitor benzamil (10(-6) mol/L) prevented both CTGF and its stimulation by Ang II. We concluded that Ang II in the CNT lumen enhances CTGF via activation of Ang II type 1 and that this effect requires activation of protein kinase C and ENaC. Potentiation of CTGF by Ang II could help preserve glomerular filtration rate in the presence of renal vasoconstriction.
Ren
Yilin
Y
Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, Detroit, MI 48202, USA.
D'Ambrosio
Martin A
MA
Garvin
Jeffrey L
JL
Carretero
Oscar A
OA
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D057912:Angiotensin II Type 2 Receptor Blockers; D000818:Animals; D001160:Arterioles / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D062686:Epithelial Sodium Channel Blockers; D053503:Epithelial Sodium Channels / Q000502:physiology*; D025461:Feedback, Physiological / Q000187:drug effects; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000098:blood supply*; D007684:Kidney Tubules / Q000098:blood supply; D019808:Losartan / Q000494:pharmacology; D008833:Microcirculation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D011817:Rabbits; D044139:Receptor, Angiotensin, Type 2 / Q000502:physiology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D012965:Sodium Chloride / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D062686:Epithelial Sodium Channel Blockers; D053503:Epithelial Sodium Channels; D007093:Imidazoles; D011725:Pyridines; D044139:Receptor, Angiotensin, Type 2; D026941:Sodium Channel Blockers; D014662:Vasoconstrictor Agents; C013407:benzamil; D000804:Angiotensin II; C073402:PD 123319; D012965:Sodium Chloride; D000584:Amiloride; D019808:Losartan