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Rat Coronary Endothelial Cell Membrane Potential Responses During Hypertension
Kathryn M. Gauthier1, Nancy J. Rusch
1Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee.
Hypertension (Dallas, Tex. : 1979)
|February 24, 2001
Summary
Coronary arteries in hypertensive rats maintain normal acetylcholine-induced dilation but show impaired responses to substance P and bradykinin, indicating selective dysfunction in specific signaling pathways.
Area of Science:
- Cardiovascular Physiology
- Renal Hypertension Research
- Endothelial Cell Biology
Background:
- Hypertension can alter vascular function in coronary arteries.
- Endothelial cell membrane potential plays a crucial role in regulating vascular tone.
- Previous studies have not fully characterized membrane potential changes in coronary endothelial cells during hypertension.
Purpose of the Study:
- To investigate and compare membrane potential profiles in coronary endothelial cells of normotensive and hypertensive rats.
- To assess the impact of hypertension on dilator responses mediated by acetylcholine, substance P, and bradykinin.
- To correlate endothelial cell membrane potential changes with vascular smooth muscle relaxation in a rat model of hypertension.
Main Methods:
- Utilized the 1-kidney, 1-clip rat model to induce renal hypertension.
- Employed cannulated coronary arteries for assessing dilator responses.
- Applied the perforated patch-clamp technique to measure membrane potential in intact endothelial cells.
Main Results:
- Acetylcholine induced similar large dilations and hyperpolarizing responses in coronary arteries from both control and hypertensive rats.
- Substance P and bradykinin caused significant dilations and hyperpolarizations in control rats, but these responses were blunted in hypertensive rats.
- Dilations to substance P and bradykinin in hypertensive rats were largely independent of significant membrane potential changes.
Conclusions:
- Coronary endothelial cell hyperpolarizing responses to acetylcholine remain intact in the 1-kidney, 1-clip model of hypertension.
- Dilator responses to substance P and bradykinin are selectively impaired in the coronary arteries of hypertensive rats.
- Hypertension differentially affects endothelial-dependent vasodilation, targeting pathways not solely reliant on large membrane potential shifts.