angiotensinogen and Renal-Artery-Obstruction

Genes that influence the renin-angiotensin system have been investigated in recent years as potential etiologic candidates of cardiovascular and renal diseases. In atheromatous renal artery stenosis (RAS), a condition characterized by persistent activation of the renin-angiotensin system, the study of these genes may be of particular relevance. We evaluated angiotensin-converting enzyme (ACE) insertion/deletion, angiotensinogen (AGT) M235T, and angiotensin II receptor (ATR) A1166C polymorphisms in relation to the occurrence of RAS. We studied 58 patients with angiographically documented RAS; 102 normotensive subjects with normal coronary arteries and no history or clinical or instrumental evidence of atherosclerosis in other vascular districts were considered the control group. Patients had a significantly higher D allele frequency (0.70 versus 0.55; chi(2) 6.88, P=0.01; odds ratio [OR] 1. 9, 95% CI 1.17 to 3.07) than did the control population; 48.3% of patients were homozygous for DD (chi(2) 6.62, P<0.05; OR 2.04, 95% CI 1.05 to 3.95); and only 8.6% carried the II genotype (OR 0.34, 95% CI 0.19 to 1.47). No significant association was found for AGT M235T and ATR A1166C. Our results suggest a predisposing role for ACE genetic polymorphism in the development and progression of atheromatous RAS.

Topics: Adult; Aged; Alleles; Angiotensinogen; Arteriosclerosis; Female; Genotype; Humans; Male; Middle Aged; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Receptors, Angiotensin; Renal Artery Obstruction

In 22 hypertensive patients with unilateral renal artery stenosis (RAS) and in 8 patients with unilateral or bilateral renal or renal arterial disease, plasma renin activity (PRA), renin substrate (PRS), and angiotensin II (AT II) concentrations were measured in both renal veins and in a peripheral vein 1-2 h after stimulation of renin secretion by injection of frusemide. In patients with elevated PRA in venous blood from a kidney with RAS, AT II was either also elevated, lower than or equal to PRA in peripheral blood, while the contralateral kidney almost invariably extracted AT II. In the 8 patients with variable renal diseases, the concordance between PRA and AT II measurements was better. Results suggest that AT II measurements in renal venous blood are less useful in assessing the functional significance of a RAS than those of PRA. Since PRS is not different in venous plasma of the diseased and the normal kidney, PRA measurements can be regarded as proportional to plasma renin concentration in this condition.

Topics: Adult; Aged; Angiotensin II; Angiotensinogen; Blood Pressure; Female; Furosemide; Humans; Hypertension, Renal; Male; Middle Aged; Renal Artery Obstruction; Renal Veins; Renin; Stimulation, Chemical; Vena Cava, Inferior

The rate of angiotensin generation with added renin in plasma from patients with benign essential hypertension has been shown to be higher than in plasma from norm ensive controls. An index of the angiotensin generation rate in relation to to al plasma renin substrate (PRS-r index) has been defined which allows for screening for "activated" plasma. In hypertensive subjects, this index was shown to be higher than that of the normotensive subjects (61 plus or minus 2.4 SE, and 45 plus or minus 5 SE). The index did not correlate with the absolute levels of blood pressure, 24-hour sodium excretion, or plasma renin activity in hypertensive subjects either during the control period or during acute alterations of blood pressure, but was shown to respond in a parallel fashion with chronically induced changes in blood pressure and circulating levels of angiotensin I. By the use of an isolated system of human renin and homologous renin substrate, we have demonstrated that plasma from hypertensive subjects contains a modifier of the renin reaction which increases both V-max and Km of the system, behaving as an uncompetitive activator. No significant change was noted with the addition of normal plasma to the same isolated system.

Topics: Angiotensin II; Angiotensinogen; Animals; Blood Pressure; Contraceptives, Oral; Diuretics; Enzyme Activation; Functional Laterality; Haplorhini; Humans; Hydrochlorothiazide; Hypertension; In Vitro Techniques; Kinetics; Renal Artery Obstruction; Renin; Sodium; Spironolactone

The relationship between plasma renin activity (PRA), angiotensin II (AT II) and renin substrate concentration (PRS) were studied in a patient with left renal artery occlusion and malignant hypertension before and after left-side nephrectomy. Initially, PRA and AT II were grossly elevated, while PRS was low. Treatment with alpha-methyl-DOPA and saline led to a fall in PRA and AT II and a large rise in PRS. The correlation between PRA and AT II (r=0.937; n=9, p less than 0.001) was highly significant. PRA and PRS were negatively correlated before operation (r=-0.78; n=6; p less than 0.05). A comparison of changes in PRS before and after nephrectomy suggests that renin substrate formation was increased when the ischemic kidney was still in situ. Following nephrectomy, PRA and blood pressure fell to normal within 5 hours, while PRS remained unchanged for this period of time. A two-compartmental analysis of the renin disappearance curve after nephrectomy revealed the presence of a fast and slow component with half-lives of 10 and 95 min, respectively.

Topics: Angiotensin II; Angiotensinogen; Humans; Hypertension, Malignant; Hypertension, Renal; Male; Middle Aged; Nephrectomy; Renal Artery Obstruction; Renin