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Cilnidipine improves spontaneously hypertensive rat coronary hemodynamics without altering cardiovascular mass and
Jasmina Varagic1, Dinko Susic, Edward D Frohlich
1Hypertension Research Laboratory, Alton Ochsner Medical Foundation, New Orleans, Louisiana 70121, USA.
Insights
Cilnidipine, a novel calcium channel blocker, improved coronary hemodynamics in spontaneously hypertensive rats without affecting cardiovascular structure. This suggests potential benefits for managing hypertension-related heart conditions.
Area of Science:
- Pharmacology
- Cardiovascular Physiology
- Hypertension Research
Background:
- Spontaneously hypertensive rats (SHR) exhibit cardiovascular changes relevant to human hypertension.
- Dihydropyridine calcium channel blockers are widely used for hypertension treatment.
- Cilnidipine uniquely blocks both L-type and N-type calcium channels.
Purpose of the Study:
- To investigate the long-term effects of cilnidipine on hemodynamics, cardiovascular mass, and collagen in WKY and SHR rats.
- To assess cilnidipine's impact on systemic, regional, and coronary circulation.
- To determine if cilnidipine alters cardiac and vascular structure in hypertensive models.
Main Methods:
- Male WKY and SHR rats received cilnidipine (10 mg/kg/day) or no treatment for 12 weeks.
- Systemic and regional hemodynamics were measured using radionuclide-labeled microspheres.
- Left and right ventricular and aortic mass, and hydroxyproline concentration were analyzed.
Main Results:
- Cilnidipine did not alter hemodynamics, mass, or collagen in normotensive WKY rats.
- In SHR, cilnidipine reduced arterial pressure and total peripheral resistance, without affecting heart rate or cardiac index.
- Coronary vascular resistance in the left ventricle was reduced by cilnidipine in SHR, with further decrease after dipyridamole administration.
Conclusions:
- Cilnidipine, an L- and N- type calcium channel antagonist, demonstrates beneficial effects on coronary hemodynamics in SHR.
- These effects occur without adverse changes in cardiovascular mass or collagen content.
- Cilnidipine shows promise for managing hypertensive cardiovascular complications.
Objective:
The present study was designed to determine the effects of prolonged treatment with cilnidipine, a novel dihydropyridine calcium antagonist which blocks both L-type and N-type calcium channels, on systemic, regional and coronary hemodynamics, cardiovascular mass and collagen content in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats.
Methods:
Male 23-week-old WKY and SHR rats were divided into two groups for each strain. One group received cilnidipine (10 mg/kg per day), whereas their respective controls were given no therapy. Systemic and regional hemodynamics (radionuclide-labeled microspheres), left and right ventricular and aortic mass, and hydroxyproline concentration were determined after 12 weeks treatment.
Results:
The data demonstrated that cilnidipine neither affected systemic hemodynamics nor cardiovascular mass and collagen content in WKY rats. The same treatment in the SHR reduced arterial pressure and total peripheral resistance without changes in heart rate and cardiac index. Ventricular and aortic mass indices as well as ventricular collagen content remained unchanged. There were no differences in organ blood flows between two SHR groups, whereas renal, liver and left ventricular coronary vascular resistances were reduced by cilnidipine. After dipyridamole infusion left ventricular minimal coronary vascular resistance decreased further in cilnidipine-treated SHR as compared with control SHR rats.
Conclusion:
These data suggest that cilnidipine, an L- and N- type calcium channel antagonist, exerted beneficial effects on coronary hemodynamics without altering cardiovascular mass or collagen content in SHR.
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