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1 Endothelin-1 (ET-1), endothelin-3 (ET-3) and noradrenaline (NA) were administered as intra-arterial bolus injections into the isolated, blood-perfused spleen of the dog to assess agonist properties and relative molar potencies on the vascular and capsular smooth muscle. 2 An initial small vasodilatation was observed occasionally at low doses (1.0-i0pmol) of ET-1. 3 ET-1, ET-3 and NA all caused graded increases in splenic arterial vascular resistance. The molar ED50 for the splenic vasoconstrictor response to ET-1 was significantly less (P < 0.001) than that to ET-3; both peptides were significantly more potent as vasoconstrictor agents than NA. The maximum increase in splenic arterial vascular resistance was not significantly different for either ET-1, The time course of the splenic vasoconstrictor response to ET-1 was significantly (P < 0.01) longer than that to equieffective doses of ET-3 or NA. 5 The splenic vasoconstrictor responses to ET-1 and ET-3 were accompanied by reductions in spleen volume. The rank order of molar potency in causing splenic capsular contraction was ET-i > ET-3 > NA. The maximum reduction in splenic volume was significantly greater for NA than for either ET-i or ET-3. The two peptides (ET-1, ET-3) were equiefficacious in contracting splenic capsular smooth muscle. 6 The high molar potency of ET-1 as a splenic arterial vasoconstrictor, over 1,700 times more potent than NA, suggests that it may play an important local role in the control of splenic haemodynamics.

Background Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder, and the underlying causes remain unknown and have not been fully elucidated. Several candidate genes have been associated with T2DM in various populations with conflicting results. The variations found in glucokinase (GCK), glucokinase regulatory protein (GCKR), and glucose-6-phosphatase 2 (G6PC2) genes were not well studied, particularly among Asians. Aims The main objective of this study was to determine the candidate genetic polymorphisms of GCK (rs1799884), GCKR (rs780094), and G6PC2 (rs560887) genes in T2DM among Malay ethnics. Methods In this candidate gene association study, a total of 180 T2DM subjects and 180 control subjects were recruited to determine the genotypes using polymerase chain reaction-restriction fragment length polymorphism and Taqman probe assay methods. Genotype and allele frequencies in case and control samples were compared using the chi-squared test to determine a significant difference. Results The body mass index, fasting blood glucose, hemoglobin A1c, systolic and diastolic blood pressure, and total cholesterol were significantly different (p < 0.05) between T2DM and control subjects. The genotypic and allelic frequencies of GCK (rs1799884), GCKR (rs780094), and G6PC2 (rs560887) gene polymorphisms were significantly different between T2DM and controls (p < 0.05). Conclusion Hence, rs1799884 of GCK gene and rs780094 of GCKR gene and rs560887 of the G6PC2 gene are possible genetic biomarkers in T2DM development among Malay ethnics in Malaysia.

Objectives. Endothelin-1 (ET-1), the most potent endogenous vasoconstrictor, generated by enzymatic cleavage catalyzed by an endothelin-converting enzyme (ECE), plays a significant role in the regulation of hypertension. Methods. This study investigates the effect of endothelin-1 (Lys198Asn/rs5370) and ECE (rs212526 C/T) gene polymorphisms with essential hypertension (EH) among Malay ethnics. To determine the association of gene polymorphism, 177 hypertensives and controls (196) were genotyped using Taqman method. Results. A significant difference was observed in ET-1 rs5370 and ECE rs212526 gene polymorphisms between EH and control subjects ( P < 0.001 ). A significantly high body mass index (BMI), waist-to-hip ratio, fasting plasma glucose, hemoglobin A1c, systolic and diastolic blood pressure, and lipid profiles were observed among the EH patients when compared to controls ( P < 0.05 ). Moreover, T allele (rs5370) carriers in males have a high risk for EH. There was no significant association between gender in ECE C/T polymorphisms ( P > 0.05 ). Conclusion. Based on our result, it is evident that the T allele of ET-1 rs5370 polymorphism and C allele of ECE rs212526 have a significant genetic risk factor in EH among Malay subjects, and BMI and age are associated with hypertension.