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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.
Insights
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.
Abstract:
-The purpose of this study was to provide the first membrane potential profile in coronary endothelial cells from normotensive sham-operated control and 1-kidney, 1-clip renal hypertensive rats. Dilator responses were assessed in cannulated coronary arteries from control and 1-kidney, 1-clip rats, and the perforated patch-clamp method was used to compare membrane potential responses between the intact endothelial cells. Under these conditions, acetylcholine (100 pmol/L to 10 µmol/L) induced similar large dilations of coronary arteries from control and 1-kidney, 1-clip rats that were associated with endothelial cell hyperpolarizing responses of 16+/-3 and 18+/-2 mV, respectively. Substance P (10 fmol/L to 1 nmol/L) and bradykinin (100 fmol/L to 10 nmol/L) also substantially dilated coronary arteries from control rats but only induced small (2 to 4 mV) endothelial cell hyperpolarizing responses. These dilations, which appeared independent of membrane potential changes, were highly blunted or absent in arteries from 1-kidney, 1-clip rats. Thus, dilator responses to acetylcholine that are associated with large endothelial hyperpolarizing responses are normal in the small coronary arteries of 1-kidney, 1-clip rats. However, dilator response to substance P and bradykinin, which apparently are not heavily dependent on endothelial cell hyperpolarizations, are selectively targeted for impairment in the coronary arteries of this model of hypertension