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Clemizole and La3+ salts ameliorate angiotensin II-induced glomerular hyperpermeability in vivo
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- Dolinina, Julia (author)
- Lund University,Lunds universitet,Njurmedicin,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Njurfysiologi och peritonealdialys,Forskargrupper vid Lunds universitet,Nephrology,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine,Renal physiology and peritoneal dialysis,Lund University Research Groups
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- Rippe, Anna (author)
- Lund University,Lunds universitet,Njurmedicin,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Njurfysiologi och peritonealdialys,Forskargrupper vid Lunds universitet,Nephrology,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine,Renal physiology and peritoneal dialysis,Lund University Research Groups
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- Öberg, Carl M. (author)
- Lund University,Lunds universitet,Njurmedicin,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Njurfysiologi och peritonealdialys,Forskargrupper vid Lunds universitet,Nephrology,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine,Renal physiology and peritoneal dialysis,Lund University Research Groups
- (creator_code:org_t)
- 2021-05-27
- 2021
- English.
- In: Physiological Reports. - : Wiley. - 2051-817X. ; 9:10
- Journal article (peer-reviewed)
Abstract
Subject headings
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- Angiotensin II (Ang II) induces marked, dynamic increases in the permeability of the glomerular filtration barrier (GFB) in rats. After binding to its receptor, Ang II elicits Ca2+ influx into cells, mediated by TRPC5 and TRPC6 (transient receptor potential canonical type 5 and 6). Clemizole and La3+ salts have been shown to block TRPC channels in vitro, and we therefore tested their potential effect on Ang II-induced glomerular hyperpermeability. Anesthetized male Sprague-Dawley rats were infused with Ang II (80 ng kg–1min–1) alone, or together with clemizole or low-dose La3+ (activates TRPC5, blocks TRPC6) or high-dose La3+ (blocks both TRPC5 and TRPC6). Plasma and urine samples were taken during baseline and at 5 min after the start of the infusions and analyzed by high-performance size-exclusion chromatography for determination of glomerular sieving coefficients for Ficoll 10–80 Å (1–8 nm). Ang II infusion evoked glomerular hyperpermeability to large Ficolls (50–80 Å), which was ameliorated by clemizole, having no significant effect on glomerular filtration rate (GFR) or Ang II-mediated increase in mean arterial pressure (ΔMAP). In contrast, high- and low-dose La3+ significantly lowered ΔMAP and reduced Ang II-induced hyperpermeability. Combined, clemizole and low-dose La3+ were less effective at ameliorating Ang II-induced glomerular hyperpermeability than low-dose La3+ alone. In conclusion, our data show that both clemizole and La3+ are effective against Ang II-induced glomerular hyperpermeability, with differential effects on blood pressure. Further research using more specific blockers of TRPC5 and TRPC6 should be performed to reveal the underlying mechanisms.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)
Keyword
- Glomerular permeability
- TRPC5
- TRPC6
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- art (subject category)
- ref (subject category)
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