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The haemodynamic profile of cromakalim in the cat
1Beecham Pharmaceuticals, Medicinal Research Centre, Harlow, U.K.
Insights
Cromakalim, a novel antihypertensive, effectively lowers blood pressure by reducing total peripheral resistance with minimal heart rate increase. This agent also shows a beneficial effect on renal blood flow in cats.
Area of Science:
- Pharmacology
- Cardiovascular Physiology
Background:
- The development of novel antihypertensive agents is crucial for managing cardiovascular diseases.
- Understanding the haemodynamic effects of new drugs is essential for assessing their therapeutic potential.
Purpose of the Study:
- To investigate the haemodynamic profile of cromakalim (BRL 34915), a novel antihypertensive agent.
- To evaluate the effects of cromakalim on arterial pressure, cardiac output, and renal blood flow in feline models.
Main Methods:
- Haemodynamic parameters were assessed in conscious and anaesthetised cats.
- Cromakalim was administered orally and intravenously at various doses.
- Measurements included arterial pressure, total peripheral resistance, cardiac output, heart rate, stroke volume, and mean renal blood flow.
Main Results:
- Cromakalim significantly reduced arterial pressure and total peripheral resistance in both conscious and anaesthetised cats.
- Cardiac output increased due to augmented stroke volume, with minimal changes in heart rate at moderate blood pressure reductions.
- Mean renal blood flow increased at hypotensive doses, and cardiac contractility was enhanced with intravenous administration.
Conclusions:
- Cromakalim effectively lowers arterial pressure by decreasing total peripheral resistance with a favourable haemodynamic profile.
- The drug demonstrates a potentially beneficial effect on renal blood flow, suggesting a promising role in antihypertensive therapy.
Abstract:
The haemodynamic profile of the novel antihypertensive agent, cromakalim (BRL 34915), has been studied in conscious and anaesthetised cats. Given orally (0.03 and 0.06 mg/kg) to conscious cats and by intravenous infusion (0.002 mg/kg/min for 7-10 min) to anaesthetised animals, cromakalim reduced arterial pressure (AP; systolic/diastolic) and total peripheral resistance (TPR) while increasing cardiac output (CO) via both its components [heart rate (HR) and stroke volume (SV)]. In both models, HR changes were minimal for reductions of AP approaching 20 mm Hg. In a second group of conscious cats, cromakalim increased mean renal blood flow (MRBF) at hypotensive doses (0.03 and 0.06 mg/kg orally); HR was only significantly raised following the higher dose of cromakalim. In anaesthetised animals, intravenously infused cromakalim had little effect on central venous pressure and increased cardiac contractility. The data indicate that cromakalim lowers AP by reducing TPR with minimal increase in HR. In addition, cromakalim has a potentially beneficial effect on MRBF.