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Alterations of calcium uptake in renovascular hypertensive rat aorta: functional assessment with thapsigargin
1Laboratory of Pharmacology, College of Pharmaceutical Sciences, University of São Paulo, Ribeirão Preto, Brazil.
Insights
Hypertension in 1 kidney-1 clip (1K-1C) rats impairs calcium (Ca2+) regulation in the aorta. This defect in sarcoplasmic reticulum (SR) Ca2+-ATPase function may contribute to inadequate SR buffering, impacting vascular tone.
Area of Science:
- Cardiovascular Physiology
- Renal Hypertension
- Cellular Calcium Signaling
Background:
- Hypertension is associated with vascular dysfunction.
- Sarcoplasmic reticulum (SR) calcium (Ca2+) handling is crucial for vascular smooth muscle contraction.
- Defects in SR Ca2+-ATPase may impair vascular function in hypertensive states.
Purpose of the Study:
- To investigate the role of SR Ca2+-ATPase in impaired Ca2+ recycling in the aorta of 1 kidney-1 clip (1K-1C) hypertensive rats.
- To test the hypothesis of defective intracellular Ca2+ regulation in 1K-1C rat aortae.
Main Methods:
- Comparison of contractile responses in aortae from 1K-1C and control (1K) rats.
- Assessment of Ca2+ release from SR using phenylephrine and caffeine in Ca2+-free solution.
- Evaluation of SR Ca2+ store depletion and refilling.
- Pharmacological inhibition of SR Ca2+-ATPase using thapsigargin.
Main Results:
- 1K-1C rat aortae exhibited greater Ca2+ release-mediated contractions compared to 1K rats.
- This difference was abolished after intracellular Ca2+ store depletion and reloading.
- Thapsigargin reduced phasic contractions in both groups but increased tonic contraction during refilling in 1K-1C aortae.
Conclusions:
- The 1K-1C rat aorta demonstrates defective intracellular Ca2+ regulation.
- Impaired SR Ca2+-ATPase function contributes to inadequate SR buffering capacity in hypertension.
- These findings suggest a mechanism for vascular dysfunction in 1K-1C hypertensive rats.
Abstract:
1. The aim of this study was to test the hypothesis that impaired calcium (Ca2+) recycling by sarcoplasmic reticulum (SR) Ca2+-ATPase takes place in aortae from 1 kidney-1 clip (1K-1C) hypertensive rats. 2. The contractile response elicited when Ca2+ is released from the SR with phenylephrine and caffeine in Ca2+-free Krebs solution was greater in 1K-1C than in 1K rat aorta. In the arteries submitted to intracellular Ca2+ store depletion and reloading, this response was not different between 1K-1C and 1K rat aortae. Thapsigargin decreased the phasic contractile responses to phenylephrine in 1K and 1K-1C rat aortae and increased the tone that developed during the refilling period in 1K-1C rat aortae. 3. Our data support the hypothesis that the 1K-1C rat aorta has defective intracellular Ca2+ regulation that may be implicated in an inadequate SR buffering ability.