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Arterial structural changes with verapamil in spontaneously hypertensive rats
1Department of Internal Medicine and INSERM U337, Broussais Hospital, Paris, France.
Insights
Reducing pulse pressure, not mean arterial pressure, may reverse vascular hypertrophy in hypertensive rats. This study suggests pulse pressure is key to preventing vascular remodeling.
Area of Science:
- Cardiovascular Physiology
- Vascular Biology
- Pharmacology
Background:
- Vascular hypertrophy is a hallmark of hypertension.
- The role of pulse pressure versus mean arterial pressure in vascular remodeling is unclear.
- Conduit artery changes in spontaneously hypertensive rats (SHR) are not well-studied.
Purpose of the Study:
- To investigate if reducing pulse pressure, rather than mean arterial pressure, reverses vascular hypertrophy.
- To examine the effects of verapamil on vascular structure in SHR.
- To correlate pulse pressure with vascular remodeling in hypertensive animals.
Main Methods:
- Treatment of 4-week-old SHR with verapamil (50 mg/kg) for 16 weeks.
- Comparison with untreated SHR and normotensive Wistar Kyoto (WKY) rats.
- Measurement of blood pressure, carotid artery diameter and stiffness, and aortic histomorphometry.
Main Results:
- Verapamil significantly reduced pulse pressure but not mean arterial pressure in SHR.
- Carotid artery diameter, medial thickness, and collagen content decreased in verapamil-treated SHR.
- A positive correlation was found between pulse pressure and medial thickness.
Conclusions:
- Verapamil prevented vascular structural changes in SHR without altering mean arterial pressure.
- Pulse pressure reduction may be more critical than mean arterial pressure reduction for preventing vascular remodeling.
- Mechanosensitive elements in the vascular wall may respond to dynamic pressure changes, influencing remodeling.
Abstract:
Reducing pulse pressure might be more powerful than reducing mean arterial pressure to obtain regression of vascular hypertrophy. However, this hypothesis has never been investigated in the conduit arteries of intact hypertensive animals. A group of 4-week-old spontaneously hypertensive rats (SHR) was treated with the calcium-entry blocker verapamil (50 mg/kg) for 16 weeks and compared with untreated SHR and control Wistar Kyoto (WKY) normotensive rats of the same age. At the end of the experiment, intraarterial thoracic aorta blood pressure was measured both in the conscious and anesthetized animals. Carotid artery diameter and stiffness (echo-tracking techniques) and aortic histomorphometry were determined in parallel. With verapamil, pulse pressure, but not mean arterial pressure, was significantly decreased but did not reach the normotensive values. Carotid internal diameter, medial thickness, and collagen content were significantly reduced by comparison with SHR and did not differ from the values of the WKY group. A significant positive and independent correlation was observed between pulse pressure and medial thickness in the overall population. The study shows that, in SHR chronically treated with verapamil, structural changes may be completely prevented without any change in mean arterial pressure. The parallel change in pulse pressure might suggest that mechanosensitive elements within the vascular wall may be selectively sensitive to the dynamic aspects of physical forces and are able to convert frequency and amplitude information into cellular responses that lead to vascular remodeling.