The influence of transmural pressure and longitudinal stretch on K+– and Ca2+–induced coronary artery constriction
Abstract:The aim of the study was to investigate transmural pressure and longitudinal stretch modulation of K+- and Ca2+-induced constriction of porcine conductance coronary arteries. In a pressure myograph set-up, left anterior descendent coronary arteries from 70 to 90 kg pigs were investigated at pressures from 20 to 120 mmHg. Longitudinal extension ratio (λ = L/L0–1, where L0 is the in situ length and L the examination length) varied between 0.9 and 1.1. Two protocols were carried out: (1) Outer diameter response to maximal depolarization by K+ 125 mM at 20–120 mmHg and λ at 0.90–1.10. (2) Concentration–response curves with K+ (4.7–125 mM) and Ca2+ (0.05–4.0 mM) at four combinations of P and λ (P = 100 mmHg, λ = 0.9; P = 100 mmHg, λ = 1.1; P = 40 mmHg, λ = 0.9; p = 40 mmHg, λ = 1.1). Results: Endothelial function was preserved. A slight (<5% diameter reduction) basal tone and no myogenic response was found. Protocol 1: the constriction to K+ 125 mMwas maximal in a wide pressure range from 40 to 120 mmHg. Despite the fact that K+-induced diameter changes were statistically insignificant between 40 and 120 mmHg, there was a linear trend towards smaller diameter changes in this pressure range (r = –0.54, P < 0.01). Stretch influenced constriction at 20 mmHg because λ = 0.90 and 0.95 resulted in smaller diameter-reductions than λ = 1.00–1.10 (P < 0.05 for all). Contrastingly, at 120 mmHg the constriction at λ = 1.10 was smaller than the responses at λ = 0.90–1.05 (P < 0.05 for all). Protocol 2: EC50 and EC10 values for K+- and Ca2+ were generally higher (more sensitive) at 40 compared with 100 mmHg. Stretch was of no significant importance for EC50 and EC10 at 40 and 100 mmHg. It is concluded that porcine coronary artery constriction to non-metabolized agonists is maximal at 40 mmHg with a trend towards smaller diameter changes with higher pressures. Longitudinal stretch affects responsiveness at pressure extremes.
Document Type: Research Article
Affiliations: 1: Department of Cardiology, University Hospital Aarhus, Skejby Sygehus, Aarhus, Denmark 2: Institute of Pharmacology, University of Aarhus, Aarhus, Denmark 3: Imperial College School of Medicine, Department of Cardiology, Hammersmith Hospital, London, UK
Publication date: April 1, 1999