Pentosan polysulfate treatment preserves renal autoregulation in ANG II-infused hypertensive rats via normalization of P2X 1 receptor activation

Zhengrong Guan, Barry S Fuller, Tatsuo Yamamoto, Anthony K. Cook, Jennifer S. Pollock, Edward W. Inscho

Research output: Contribution to journalArticle

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Abstract

Inflammatory factors are elevated in animal and human subjects with hypertension and renal injury. We hypothesized that inflammation contributes to hypertension-induced renal injury by impairing auto-regulation and microvascular reactivity to P2X 1 receptor activation. Studies were conducted in vitro using the blood-perfused juxtamedullary nephron preparation. Rats receiving ANG II (60 ng/min) infusion were treated with the anti-inflammatory agent pentosan polysulfate (PPS) for 14 days. The magnitude and progression of hypertension were similar in ANG II and ANG II+PPS-treated rats (169 ± 5 vs. 172 ± 2 mmHg). Afferent arterioles from control rats exhibited normal autoregulatory behavior with diameter decreasing from 18.4 ± 1.6 to 11.4 ± 1.7 μm when perfusion pressure was increased from 70 to 160 mmHg. In contrast, pressure-mediated vasoconstriction was markedly attenuated in ANG II-treated rats, and diameter remained essentially unchanged over the range of perfusion pressures. However, ANG II-treated rats receiving PPS exhibited normal autoregulatory behavior compared with ANG II alone rats. Arteriolar reactivity to ATP and β,γ-methylene ATP was significantly reduced in ANG II hypertensive rats compared with controls. Interestingly, PPS treatment preserved normal reactivity to P2 and P2X 1 receptor agonists despite the persistent hypertension. The maximal vasoconstriction was 79 ± 3 and 81 ± 2% of the control diameter for ATP and β,γ-methylene ATP, respectively, similar to responses in control rats. PPS treatment significantly reduced α-smooth muscle actin staining in afferent arterioles and plasma transforming growth factor-β1 concentration in ANG II-treated rats. In conclusion, PPS normalizes autoregulation without altering ANG II-induced hypertension, suggesting that inflammatory processes reduce P2X 1 receptor reactivity and thereby impair autoregulatory behavior in ANG II hypertensive rats.

Original languageEnglish (US)
Pages (from-to)F1276-F1284
JournalAmerican Journal of Physiology - Renal Physiology
Volume298
Issue number5
DOIs
StatePublished - May 1 2010

Fingerprint

Pentosan Sulfuric Polyester
Homeostasis
Kidney
Adenosine Triphosphate
Renal Hypertension
Arterioles
Hypertension
Vasoconstriction
Pressure
Perfusion
Nephrons
Wounds and Injuries
Transforming Growth Factors
Smooth Muscle
Actins
Anti-Inflammatory Agents

Keywords

  • Afferent arteriole
  • P2X purinoceptor
  • Pentosan polysulfate

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Pentosan polysulfate treatment preserves renal autoregulation in ANG II-infused hypertensive rats via normalization of P2X 1 receptor activation. / Guan, Zhengrong; Fuller, Barry S; Yamamoto, Tatsuo; Cook, Anthony K.; Pollock, Jennifer S.; Inscho, Edward W.

In: American Journal of Physiology - Renal Physiology, Vol. 298, No. 5, 01.05.2010, p. F1276-F1284.

Research output: Contribution to journalArticle

Guan, Zhengrong ; Fuller, Barry S ; Yamamoto, Tatsuo ; Cook, Anthony K. ; Pollock, Jennifer S. ; Inscho, Edward W. / Pentosan polysulfate treatment preserves renal autoregulation in ANG II-infused hypertensive rats via normalization of P2X 1 receptor activation. In: American Journal of Physiology - Renal Physiology. 2010 ; Vol. 298, No. 5. pp. F1276-F1284.
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