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Updated: Jul 17, 2026
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Assessment of Vascular Tone Responsiveness using Isolated Mesenteric Arteries with a Focus on Modulation by Perivascular Adipose Tissues
Published on: June 3, 2019
Pkd2+/- vascular smooth muscles develop exaggerated vasocontraction in response to phenylephrine stimulation
Qi Qian1, Larry W Hunter, Hui Du
1Department of Medicine and Physiology, Eisenberg S-24, Nephrology, Mayo Clinic College of Medicine, 200 First Street, SW, Rochester, MN 55905, USA. qian.qi@mayo.edu
Journal of the American Society of Nephrology : JASN
|January 5, 2007
Summary
Vascular complications in autosomal dominant polycystic kidney disease are linked to abnormal blood vessel function. Pkd mutant vessels show exaggerated contractile responses to phenylephrine due to Ca(2+)-independent mechanisms and increased contractile proteins.
Area of Science:
- Cardiovascular Biology
- Renal Pathophysiology
- Vascular Smooth Muscle Physiology
Background:
- Vascular complications are a major cause of death in autosomal dominant polycystic kidney disease (ADPKD).
- Abnormal vascular reactivity is suspected in ADPKD, but contractile function in Pkd mutant vessels remains unstudied.
- Understanding vascular dysfunction is crucial for managing ADPKD-related morbidity and mortality.
Purpose of the Study:
- To investigate the contractile function of blood vessels in a Pkd mutant model.
- To determine the mechanisms underlying altered vascular contractility in Pkd2(+/-) mice.
- To explore the role of calcium signaling and contractile protein expression in vascular abnormalities.
Main Methods:
- Isometric tension measurements of de-endothelialized aortic rings and helical strips from Pkd2(+/-) and wild-type (wt) mice.
- Assessment of contractile responses to phenylephrine (PE) and direct calcium (Ca2+) stimulation.
- Measurement of intracellular calcium ([Ca2+](i)) and phosphorylated myosin light chain levels.
- Quantitative analysis of smooth muscle alpha-actin and myosin heavy chain expression.
Main Results:
- Pkd2(+/-) aortic rings and arteries exhibited significantly higher maximum force (Fmax) and increased sensitivity to PE compared to wt.
- Pkd2(+/-) vessels showed a greater force generation relative to the intracellular calcium rise (enhanced Deltaforce/DeltaCa2+ ratio).
- Elevated phosphorylated myosin light chain and increased expression of smooth muscle alpha-actin and myosin heavy chain were observed in Pkd2(+/-) vessels, indicating enhanced Ca2+-independent mechanisms.
Conclusions:
- The arterial vasculature in Pkd2(+/-) mice displays an exaggerated contractile response and heightened sensitivity to alpha1-adrenergic stimulation.
- Enhanced Ca2+-independent force generation and increased contractile protein expression contribute to vascular abnormalities in ADPKD.
- These findings highlight a novel mechanism of vascular dysfunction in ADPKD, potentially contributing to cardiovascular complications.
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