Angiotensin converting enzyme insertion/deletion polymorphism does not influence postcardiac transplantation hypertension onset or progression.
ABSTRACT The angiotensin converting enzyme insertion deletion polymorphism (ACE I/D) has been associated with much cardiovascular pathology, including posttransplantation hypertension. Hypertension is a significant cause of morbidity and mortality after cardiac transplantation. We investigated the influence of the ACE I/D polymorphism on posttransplantation hypertension.
A total of 211 heart transplant recipients and 154 corresponding donors were genotyped for the ACE I/D polymorphism by polymerase chain reaction. ACE enzymatic activity was measured by spectrophotometric kinetic analysis. Sitting systolic and diastolic blood pressures were recorded at 3 consecutive visits, and the mean was calculated. Clinical data, including demographics and medication, were collected for all recipients. Results were analyzed by the chi-square test and analysis of variance, taking a p value of <0.05 to be significant.
A total of 41.7% of the subjects were hypertensive (diastolic blood pressure >90 mm Hg) at the time of the study, with 79.6% taking at least one antihypertensive agent. We found no difference between the number of antihypertensive agents, cyclosporin dose and level, renal function, or systolic blood pressure for the different recipient or donor genotypes. We also found no significant correlation between ACE enzymatic activity and systolic or diastolic blood pressure.
Our study of 211 recipients and 154 corresponding donors is the largest investigation of this polymorphism in a cardiac transplantation population. We found no apparent relationship between the ACE genotype (of either donor or recipient) and systemic hypertension (absolute measurements and the number or dose of antihypertensive agents used).
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ABSTRACT: The effect of acute and chronic administration of cyclosporine on systemic and renal hemodynamics was studied in conscious rats. Infusion of cyclosporine in a dose of 20 mg/kg (Cy 20) resulted in a significant fall in renal blood flow (RBF) (3.4 vs. 6.5 ml/min/g, P less than 0.05) and a rise in renal vascular resistance (RVR) (36.9 vs. 20.6 mm Hg/ml/min/g, P less than 0.05). Infusion of cyclosporine at a dose of 10 mg/kg (Cy 10) did not result in a significant change in RBF or RVR. Both doses of cyclosporine resulted in stimulation of plasma renin activity (PRA) from control values of 5.6 +/- 0.8 ng/ml/hr to 11.6 +/- 2.0 with 10 mg/kg and 26.7 +/- 5.6 with 20 mg/kg. Urinary 6-keto-PGF1 alpha excretion increased from control values of 14.0 +/- 2.0 ng/6 hr to 22.7 +/- 2.2 with 10 mg/kg and 25.0 +/- 2.0 with 20 mg/kg. Similar effects on RBF, RVR, PRA, and 6-keto-PGF1 alpha excretion were seen after chronic administration of cyclosporine (20 mg/kg i.p. for 7 days). Pretreatment of animals with captopril did not prevent the fall in RBF after cyclosporine, suggesting that the vasoconstriction was not mediated by angiotensin II. Animals treated with meclofenamate demonstrated reduction in RBF with 10 mg/kg cyclosporine (4.3 vs. 7.0 ml/min/g, P less than 0.05), suggesting that prostaglandins protect against the vasoconstrictor effect of cyclosporine. Administration of phenoxybenzamine after cyclosporine improved RBF (5.0 vs. 3.4 ml/min/g) and restored RVR to normal. Similarly, renal denervation dramatically reduced the fall in RBF after cyclosporine (innervated right kidney 3.6 vs. denervated left kidney 6.0 ml/min/g, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)Kidney International 12/1985; 28(5):767-74. · 7.92 Impact Factor
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ABSTRACT: We evaluated the association between salt-sensitive hypertension and 3 different genetic polymorphisms of the renin-angiotensin system. Fifty patients with essential hypertension were classified as salt sensitive or salt resistant, depending on the presence or absence of a significant increase (P<0.05) in 24-hour ambulatory mean blood pressure (BP) after high salt intake. The insertion/deletion (I/D) angiotensin-converting enzyme (ACE) gene, the M235T angiotensinogen (AGT) gene, and the A1166C angiotensin II type 1 (AT1) receptor gene polymorphisms were determined with the use of standard polymerase chain reaction methods. Twenty-four (48%) patients with significantly increased (P<0.05) 24-hour mean BP with high salt intake (from 107.3+/-9.4 to 114.8+/-10.6 mm Hg) were classified as salt sensitive. In the remaining 26 patients (52%), high salt intake did not significantly modify 24-hour mean BP (from 107.6+/-10 to 107. 8+/-9 mm Hg), and they were classified as having salt-resistant hypertension. We did not find any significant association between either M235T AGT or A1166C AT1 receptor genotypes and the BP response to high salt intake. However, patients with essential hypertension homozygous for the insertion allele of the ACE gene (II) had a significantly higher BP increase with high salt intake (9. 8+/-8.1 mm Hg for systolic BP and 5.2+/-4.2 mm Hg for diastolic BP) than that observed in patients homozygous for the deletion allele (DD) (1.2+/-5.9 mm Hg for systolic BP; P=0.0118 and -0.2+/-4.2 mm Hg for diastolic BP; P=0.0274). Heterozygous patients (ID) exhibited an intermediate response. The prevalence of salt-sensitive hypertension also was significantly higher (P=0.012) in II (67%) and DI patients (62%) compared with DD hypertensives (19%). We conclude that a significant association exists between the I/D polymorphism of the ACE gene and salt-sensitive hypertension. Patients with II and DI genotypes have significantly higher prevalence of salt sensitivity than DD hypertensives.Hypertension 02/2000; 35(1 Pt 2):512-7. · 6.87 Impact Factor
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ABSTRACT: Fibrinolysis is controlled by the plasminogen activator system. The proteolytic activity of this system is mediated by plasmin, which is generated from plasminogen by one of two plasminogen activators. Plasminogen activator inhibitor-1 (PAI-1) inhibits this process. Individuals with reduced fibrinolytic activity are at increased risk for ischemic cardiovascular events, and reduced fibrinolysis may underlie some of the pathological consequences of reduced nitric oxide (NO) availability. Within the vasculature, angiotensin II stimulates the release of PAI-1, thereby reducing fibrinolytic activity. Thus, the plasminogen activator system is largely controlled by the renin-angiotensin system (RAS). In accordance with this finding, treatment with angiotensin converting enzyme (ACE) inhibitors is associated with substantial reductions in the incidence of ischemic cardiovascular events. Links between the RAS, fibrinolytic balance, and cardiovascular pathology are further supported by evidence from transgenic and knockout animal models. This article discusses the role of the plasminogen activator system in cardiovascular pathology, and the potential for alleviating that pathology by manipulation of the RAS.American Journal of Hypertension 02/2002; 15(1 Pt 2):3S-8S. · 3.67 Impact Factor