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[Potassium agonists: regional vasodilator profile in rats]
C Richer1, P Mulder, M P Doussau
1Département de pharmacologie, Faculté de médecine Paris-Sud, Le Kremlin-Bicêtre, France.
Archives Des Maladies Du Coeur Et Des Vaisseaux
|July 1, 1989
Summary
Potassium agonists and a calcium antagonist effectively lowered blood pressure and vascular resistance in rats. SR 44866 demonstrated potency comparable to nicardipine in reducing blood pressure.
Area of Science:
- Pharmacology
- Cardiovascular Physiology
- Hemodynamics
Background:
- Understanding the hemodynamic effects of potassium channel openers and calcium antagonists is crucial for cardiovascular drug development.
- Previous research has established the vasodilatory properties of these drug classes, but direct comparisons of their systemic and regional effects are limited.
Purpose of the Study:
- To compare the systemic and regional hemodynamic effects of two potassium agonists (cromakalim and SR 44866) and a calcium antagonist (nicardipine) in anesthetized rats.
- To determine the relative potencies of these agents in reducing blood pressure and altering vascular resistance in various vascular beds.
Main Methods:
- Anesthetized normotensive rats were administered varying doses of cromakalim, SR 44866, and nicardipine.
- Systemic and regional (kidney, mesentery, hindlimb) hemodynamics were measured using the pulsed Doppler technique.
- Blood pressure (BP), cardiac output (QC), and regional vascular resistances (TPR, MVR, RVR, HVR) were analyzed.
Main Results:
- All three drugs dose-dependently reduced BP and total peripheral resistance (TPR), with minor increases in heart rate and unchanged cardiac output.
- SR 44866 exhibited potency similar to nicardipine and significantly greater than cromakalim in lowering BP.
- At equihypotensive doses, all drugs reduced TPR, mesenteric vascular resistance (MVR), and renal vascular resistance (RVR); however, SR 44866 and nicardipine more significantly reduced hindlimb vascular resistance (HVR).
Conclusions:
- Potassium agonists and nicardipine exhibit comparable efficacy in reducing systemic and regional vascular resistance, particularly in the kidneys and mesentery.
- SR 44866 and nicardipine demonstrate a more pronounced effect on hindlimb vascular resistance compared to cromakalim.
- These findings provide valuable insights into the differential vasodilatory actions of potassium channel openers and calcium antagonists.