Differential Regulation of the Left and Right Coronary Arteries of Swine

Abstract

Coronary artery disease is one of the leading causes of myocardial infarction. Despite the predominant role of the coronary arteries in the induction of myocardial infarction, the precise contribution of each artery to this process is not well established. The present work evaluates the histological characteristics and functional properties of the left (LCA) and right (RCA) coronary arteries in swine in order to establish if the arteries are differentially regulated. To investigate this possibility, concentration-response curves for serotonin (5-HT, from 0.1 nmol/l to 100 µmol/l) and KCl (from 5 to 40 mmol/l) were performed on both arteries to determine the receptor-dependent and independent responses, respectively. The specific subtype of the 5-HT receptor involved in the contraction of both arteries was evaluated using DL-propranolol hydrochloride (5-HT₁ and nonselective β-adrenergic receptor antagonist) and ketanserine (5-HT₂ antagonist) and immunohistochemical assays. The E_max from the 5-HT concentration-response curves was 24% higher in the LCA than in the RCA (n = 59, p < 0.05). EC₅₀ values from both curves were also significantly different (LCA 0.150 ± 0.005 µmol/l and RCA 0.171 ± 0.010 µmol/l, n = 59, p < 0.05). Similarly, the E_max for KCl was 36% higher in the LCA than in the RCA (n = 9, p < 0.05), and the EC₅₀ values also differed (LCA 15.30 ± 0.06 mmol/l and RCA: 14.30 ± 0.11 mol/l, n = 9, p < 0.05). Ketanserine reduced the E_max by 63% in the LCA and by 67% in the RCA. DL-propranolol hydrochloride decreased E_max by 24% in the LCA and by 26% in the RCA. The dry weight and media area were larger in the LCA than in the RCA (17%, n = 40, p < 0.05, and 3%, n = 40, p < 0.05, respectively). Immunohistochemical assay results reveal that the average density of 5-HT_2A receptor subtype was also higher in the LCA (41.24 ± 1.35) than in the RCA (18.49 ± 1.14; n = 20, p < 0.05). Together, the findings of this study suggest that a differential physiological regulation exists between the LCA and RCA in swine. This differential regulation may have arisen as a mechanism for maintaining an adequate perfusion pressure in the wall of the left ventricle, favoring a greater oxygen delivery to match the increased oxygen demand of the left ventricle.

5-HT_1B Receptor Subtype and Aging in Rat Resistance Vessels

“…The potency order observed was: 5-HT 1 5-CT 1 sumatriptan, similar to that reported in the literature [16,17] . It was reported [17,18] that the ability of 5-HT to constrict rabbit coronary arteries is mediated by both 5-HT 1B and 5-HT 2A receptors. Our data also indicate that a mixed receptor population mediates contractile responses to 5-HT, including 5-HT 1B and 5-HT 2A receptors.…”

Serotonin Receptors in Myocardial Infarction: Friend or Foe?

“…30,55,56 Enhanced 5-HT2AR expression was detected in arteries compared to veins and in the left coronary artery compared to the right coronary artery in rats and swine, respectively. 52,115 Interestingly, although AMI has been shown to facilitate transition of cardiac fibroblasts into myofibroblasts resulting in increased expression of SERT and TPH1, it does not result in any changes in 5-HT2AR expression in these myofibroblasts. 116 Pharmacological inhibition of 5-HT2AR activity showed cardioprotective effects with repressed hypertrophic remodeling.…”

“…More recently, Williams et al demonstrated that depressed cardiovascular patients have higher 5-HT2AR density on platelets and significantly higher incidence of major and minor cardiac adverse events . Moreover, 5-HT2AR-mediated signaling can regulate the vascular tone leading to vasoconstriction. ,, Enhanced 5-HT2AR expression was detected in arteries compared to veins and in the left coronary artery compared to the right coronary artery in rats and swine, respectively. , Interestingly, although AMI has been shown to facilitate transition of cardiac fibroblasts into myofibroblasts resulting in increased expression of SERT and TPH1, it does not result in any changes in 5-HT2AR expression in these myofibroblasts …”

“…Such treatment leads to reduced receptor expression and might correlate with the degree of hypertrophy (see Figure ). , Treatment with the receptor inhibitor ketanserin led to reduced left coronary artery contraction in response to 5-HT stimulation, rendering the 5-HT2AR responsible for this reaction. , Ketanserin was further shown to improve cardiac function and angiogenesis in ischemic myocardial tissue after AMI in rats and was suggested for therapeutic treatment after AMI in humans. , In the study by Yu et al, ketanserin (0.3 mg/kg daily) was orally administered starting 2 weeks before the left coronary artery ligation and long-term treatment effects were assessed up to three month later, suggesting chronic treatment.…”