Kwan-Lih Hsu

Molecular variant M235T of the angiotensinogen gene is associated with essential hypertension in Taiwanese

Objective To examine the association of the molecular variants of the angiotensinogen (AGT) gene with essential hypertension in Taiwanese. Methods We conducted a case-control study concerning 151 subjects, 102 hypertensives and 49 normotensives. We created a rapid mini-sequencing method based on dye-terminator cycle sequencing to simultaneously detect the M235T and T174M variants of the AGT gene for each subject. Results The genotype and allele distribution of the M235T variant differed significantly in hypertensives and normotensives (χ2 = 11.106, P = 0.004 and χ2 = 6.453, P = 0.011, respectively), whereas those of the T174M variant did not differ (χ2 = 0.004, P = 0.998 and χ2 = 0.032, P = 0.858, respectively). The odds ratio for hypertension was 3.64 (95% confidence interval 1.56–8.49) for subjects with the C/C genotype of the M235T variant compared with other genotypes or 2.87 (95% confidence interval 1.76–4.68) for those carrying allele C versus those carrying allele T. Conclusion The molecular variant M235T, but not T174M, of the AGT gene is associated significantly with essential hypertension in this Taiwanese population. The genotype C/C or allele C is a risk factor for hypertension. The underlying mechanism of this association needs to be elucidated further.

Lack of association of the angiotensin converting enzyme gene polymorphism with essential hypertension in a chinese population

To examine the association between insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene and essential hypertension in a Chinese population, a case-control study was conducted using 157 hypertensive and 115 normotensive subjects. The I/D polymorphism of the ACE gene was identified by polymerase chain reaction. Plasma ACE activity was determined using spectrophotometry. The difference of allele frequencies between normotensives and hypertensives was statistically significant (chi 2 = 4.467, P = .035), while the genotype distribution was not different between normotensive and hypertensive subjects (chi 2 = 3.954, P = .138). Plasma ACE activity was highest in the DD genotype, followed by the ID genotype, and the lowest in the II genotype (P = .0001 in normotensives and P = .163 in hypertensives, respectively). Thus, we conclude that the ACE gene polymorphism is not associated with essential hypertension in this Chinese population, but plasma ACE activity is genetically determined in the normotensive Chinese.

Renin-angiotensin system gene polymorphisms and diastolic heart failure

Background  Diastolic heart failure (DHF) refers to an abnormality of diastolic distensibility, filling or relaxation of the left ventricle. The genetic study of DHF is scarce in the literature. The association of renin‐angiotensin system (RAS) and DHF are well known. We hypothesized that RAS genes might be the susceptible genes for DHF and conducted a case‐control study to prove the hypothesis.

Association of the renin gene polymorphism with essential hypertension in a Chinese population

To study the association of renin gene polymorphism with essential hypertension in the Chinese population, 86 hypertensive and 107 normotensive subjects were enrolled from an epidemiologic survey. Leukocyte DNA was extracted and digested with Hind HI and Bgl I restriction enzymes. Southern hybridization was done with digoxigenin‐incorporated renin gene probes generated by polymerase chain reaction. The restriction fragments were detected by anti‐digoxigenin antibody and enzyme methods. Two Hind III polymorphysms of the renin gene (8.7kb and 6.2kb) were identified. The allele frequences were 129(75%) and 43(25%), respectively, in hypertensives; they were 139(65%) and 75(35%), respectively, in normotensives (χ2= 4.074, p = 0.044). The genotypes of 8.7/8.7,8.7/6.2 and 6.2/6.2 were significantly different between hypertensives and normotensives, being 45(52%), 39(45%), 2(3%) and 48(45%), 43(40%), and 16(15%), respectively (χ2= 9.002, p = 0.011). The Bgl I polymorphism did not show a difference between hypertensives and normotensives. Thus, we conclude that the renin gene Hind III polymorphysm is associated with hypertension in this Chinese population.

Aminoguanidine prevents arterial stiffening and cardiac hypertrophy in streptozotocin-induced diabetes in rats

The formation of advanced glycation endproducts (AGEs) on collagen within the arterial wall may be responsible for the development of diabetic vascular injury. This study was to examine the role of aminoguanidine (AG), an inhibitor of AGEs formation, in the prevention of arterial stiffening and cardiac hypertrophy in streptozotocin (STZ) induced diabetes in rats. Diabetes was induced in animals by a single tail vein injection with 65 mg kg−1 STZ. After confirmation of the development of hyperglycemia (2 days later), rats were treated for 8 weeks with AG (daily peritoneal injections of 50 mg kg−1) and compared with the age‐matched untreated diabetic controls. After exposure to AG, the STZ‐diabetic rats showed no alterations in cardiac output, aortic pressure profiles, total peripheral resistance, and aortic characteristic impedance. By contrast, treatment of this experimental diabetes with AG resulted in a significant increase in wave transit time (τ), from 20.4±0.6 to 24.7±0.5 ms (P<0.05) and a decrease in wave reflection factor (Rf), from 0.78±0.04 to 0.53±0.02 (P<0.05). The decreased Rf associated with the increased τ suggest that AG may retard the diabetes‐induced augmentation in systolic load of the left ventricle coupled to its arterial system. Meanwhile, the diminished ratio of left ventricular weight to body weight suggests that prevention of the diabetes‐related cardiac hypertrophy by AG may correspond to the drug‐induced decline in aortic stiffening. Glycation‐derived modification on aortic collagen was also found to be enhanced in rats with diabetes (+65.3%, P<0.05) and the advanced glycation process was retarded by AG treatment. We conclude that long‐term administration of AG to the STZ‐treated rats imparts significant protection against the diabetes‐derived deterioration in vascular dynamics, at least partly through inhibition of the AGEs accumulation on collagen in the arterial wall.

Prevention of arterial stiffening by pyridoxamine in diabetes is associated with inhibition of the pathogenic glycation on aortic collagen

Background and purpose:  Our team previously demonstrated that diabetes induces a deterioration in vascular dynamics, in parallel with the enhanced formation of advanced glycation end products. The aim of this study was to determine whether prevention of the arterial stiffening by pyridoxamine in diabetes is associated with inhibition of the pathogenic glycation on aortic collagen.

Aminoguanidine prevents fructose-induced deterioration in left ventricular-arterial coupling in Wistar rats.

Aminoguanidine (AG), an inhibitor of advanced glycation endproducts, has been identified as a prominent agent that prevents the fructose‐induced arterial stiffening in male Wistar rats. Our aims were to examine whether AG produced benefits on the left ventricular (LV)‐arterial coupling in fructose‐fed (FF) animals in terms of the ventricular and arterial chamber properties.

Transcatheter embolization of a huge renal arteriovenous fistula with Amplatzer Vascular Plug

A large renal arteriovenous fistula (RAF) may lead to heart failure, renal insufficiency, hematuria, and progressive increase in size of renal vessels. Here we present the case of a 67-year-old man with a huge left RAF, who suffered from exertional dyspnea, nocturnal orthopnea, and impaired renal function. The left renal vein and inferior vena cava were dilated to 4 cm. An Amplatzer Vascular Plug with the largest size of 30 mm in disk diameter was deployed to block the fistula, with balloons inflated at renal artery and vein in advance, to reduce the renal flow in order to prevent plug migration. The decrease of shunt flow after embolization was suboptimal. However, dyspnea ameliorated, which was associated with decreased cardiac murmur, subsided abdominal bruit, normalization of the lowered diastolic pressure, and better renal function. In addition, more microcoils can be applied, using the lodged plug as a framework, to achieve the best clinical improvement.

Autonomic neuropathy precedes cardiovascular dysfunction in rats with diabetes

Background  Our team previously demonstrated arterial stiffening and cardiac hypertrophy in type 2 diabetic rats at 8 but not 4 weeks after being administered streptozotocin (STZ) and nicotinamide (NA). The present study focused on investigating the effects of type 2 diabetes on cardiac autonomic nerve function in the STZ‐ and NA‐treated animals, using modern spectral estimation technique.

Effects of Diabetes and Gender on Mechanical Properties of the Arterial System in Rats: Aortic Impedance Analysis

We determined the effects of diabetes and gender on the physical properties of the vasculature in streptozotocin (STZ)-treated rats based on the aortic input impedance analysis. Rats given STZ 65 mg/kg i.v. were compared with untreated age-matched controls. Pulsatile aortic pressure and flow signals were measured and were then subjected to Fourier transformation for the analysis of aortic input impedance. Wave transit time was determined using the impulse response function of the filtered aortic input impedance spectra. Male but not female diabetic rats exhibited an increase in cardiac output in the absence of any significant changes in arterial blood pressure, resulting in a decline in total peripheral resistance. However, in each gender group, diabetes contributed to an increase in wave reflection factor, from 0.47 ± 0.04 to 0.84 ± 0.03 in males and from 0.46 ± 0.03 to 0.81 ± 0.03 in females. Diabetic rats had reduced wave transit time, at 18.82 ± 0.60 vs 21.34 ± 0.51 msec in males and at 19.63 ± 0.37 vs 22.74 ± 0.57 msec in females. Changes in wave transit time and reflection factor indicate that diabetes can modify the timing and magnitude of the wave reflection in the rat arterial system. Meanwhile, diabetes produced a fall in aortic characteristic impedance from 0.023 ± 0.002 to 0.009 ± 0.001 mmHg/min/kg/ml in males and from 0.028 ± 0.002 to 0.014 ± 0.001 mmHg/min/kg/ml in females. With unaltered aortic pressure, both the diminished aortic characteristic impedance and wave transit time suggest that the muscle inactivation in diabetes may occur in aortas and large arteries and may cause a detriment to the aortic distensibility in rats with either sex. We conclude that only rats with male gender diabetes produce a detriment to the physical properties of the resistance arterioles. In spite of male or female gender, diabetes decreases the aortic distensibility and impairs the wave reflection phenomenon in the rat arterial system.