The meat quality of different pig breeds is associated with their different muscle tissue physiological processes, which involves a large variety of genes related with muscle fat and energy metabolism. Understanding the differences of biological processes of muscle after slaughter is helpful to reveal the meat quality development of different breeds. Therefore, eight native Large Black pigs (BP), with high fat content in meat, and seven cross-bred commercial pigs (CP), which had a high feed efficiency with high lean meat, were used to investigate the differences in their meat quality and RNA transcriptomes. The average daily gain (ADG) and hot carcass weight (HCW) of CP were higher than BP, but the back-fat thickness of BP was higher than CP (p < 0.05). The CP had higher a* (redness) but lower h (hue angle) than BP (p < 0.05). The metmyoglobin (MMb) percentage of CP was higher (p < 0.05) than BP. The fat content and oxygen consumption of longissimus dorsi (LD) muscles in BP were higher (p < 0.05) than CP. BP had higher monounsaturated fatty acids (MUFA) content, but CP had higher polyunsaturated fatty acids (PUFA) content (p < 0.05). The RNA-seq data highlighted 201 genes differentially expressed between the two groups (corrected false discovery rate (FDR) p < 0.05), with 75 up-regulated and 126 down-regulated genes in BP compared with CP using the fold change (FC). The real-time PCR was used to validate the results of RNA-seq for eight genes, and the genes related to lipid and energy metabolism were highly expressed in BP (p < 0.05). Based on the results, BP had superior intramuscular fat content to CP, while the growth performance of CP was better, and the transcriptomic differences between these two groups of pigs may cause the meat quality and growth performance variance.

Rationale:Calcium channel blockers (CCBs) exert their antihypertensive effect by reducing cardiac afterload but not preload, suggesting that Ca²⁺influx through L-type Ca²⁺channels (LTCC) mediates arterial but not venous tone.Objective:The object of this study was to resolve the mechanism of venous resistance to CCBs.Methods and Results:We compared the sensitivity of depolarization (KCl)-induced constriction of rat small mesenteric arteries (MAs) and veins (MVs) to the dilator effect of CCBs. Initial findings confirmed that nifedipine progressively dilated depolarization-induced constrictions in MAs but not MVs. However, Western blots showed a similar expression of the α_1Cpore-forming subunit of the LTCC in both vessels. Patch-clamp studies revealed a similar density of whole-cell Ca²⁺channel current between single smooth muscle cells (SMCs) of MAs and MVs. Based on these findings, we hypothesized that LTCCs are expressed but “silenced” by intracellular Ca²⁺in venous SMCs. After depletion of intracellular Ca²⁺stores by the SERCA pump inhibitor thapsigargin, depolarization-induced constrictions in MVs were blocked 80% by nifedipine suggesting restoration of Ca²⁺influx through LTCCs. Similarly, KCl-induced constrictions were sensitive to block by nifedipine after depletion of intracellular Ca²⁺stores by caffeine, ryanodine, or 2-aminoethoxydiphenyl borate. Cell-attached patch recordings of unitary LTCC currents confirmed rare channel openings during depolarization of venous compared to arterial SMCs, but chelating intracellular Ca²⁺significantly increased the open-state probability of venous LTCCs.Conclusions:We report that intracellular Ca²⁺inactivates LTCCs in venous SMCs to confer venous resistance to CCB-induced dilation, a fundamental drug property that was previously unexplained.

The anorexigen (+)-fenfluramine was used for treatment of obesity until the association of use with valvular heart disease and primary pulmonary hypertension. (+)-Fenfluramine has been found in Chinese and Korean slimming pills. The hepatic metabolite of (+)-fenfluramine, (+)-norfenfluramine, has affinity for 5-hydroxytryptamine (5-HT)_2A and 5-HT_2B receptors. We tested the hypothesis that (+)-norfenfluramine contracts arterial smooth muscle in a 5-HT receptor-dependent manner and acts as a pressor in the conscious rat. Isometric contraction experiments showed that (+)-norfenfluramine (10 nM, 100 μM) but not (+)-fenfluramine nor the isomer (-)-norfenfluramine caused concentration-dependent contraction in arteries [-log EC₅₀ (moles per liter), thoracic aorta = 5.77 ± 0.09; renal artery = 6.29 ± 0.02; mesenteric resistance artery = 5.70 ± 0.06]. Contraction was dependent on the 5-HT_2A receptor because ketanserin (10 nM) rightward shifted (+)-norfenfluramine response curves (aorta = 16-fold, renal artery = 26-fold, and resistance artery = >100-fold). Dependence on activation of 5-HT_2A receptors and independence of (+)-norfenfluramine-induced contraction from stimulation of α-adrenergic receptors and the sympathetic nervous system was validated by demonstrating 1) unchanged contraction to (+)-norfenfluramine in arteries from chemically denervated rats; 2) a minimal effect of the α₁-adrenergic receptor antagonist prazosin (100 nM) on contraction; and 3) antagonism by [6-methyl-l-(1-methylethy)ergoline-8β-carboxylic acid 2-hydroxy-1 methylpropyl ester maleate] LY53857 [6-methyl-1-(1-methylethy)-ergoline-8β-carboxylic acid 2-hydroxy-1 methylpropyl ester maleate], a 5-HT₂ receptor antagonist without α-receptor affinity. (+)-Norfenfluramine (10-300 μg/kg i.v.) caused a dose-dependent increase in mean arterial blood pressure in conscious rats, the maximum of which could be virtually abolished by ketanserin (3 mg/kg i.v.) but not prazosin (0.2 mg/kg i.v.). Our findings demonstrate for the first time that (+)-norfenfluramine is vasoactive and has the potential to increase blood pressure.