angiotensin-i and Renal-Artery-Obstruction

The role of the renin-angiotensin system in the pathogenesis of one-clip, two-kidney hypertension has been studied in man, dog and rat. Particular attention has been paid to peripheral plasma concentrations of angiotensin II in different circumstances; angiotensin II infusion has been combined with radioimmunoassay to construct angiotensin II/blood pressure dose-response curves. The effect of converting enzyme inhibitors has been studied, precautions being taken to avoid obtaining falsely high values for plasma angiotensin II because of cross-reaction with angiotensin I in these circumstances. The initial phase of one-clip, two-kidney hypertension is attributable to the direct pressor effect of the immediate rise in plasma angiotensin II. Subsequently, plasma angiotensin II is relatively lower, although blood pressure remains high. This upward resetting of the plasma angiotensin II/blood pressure relationship can be mimicked by infusing angiotensin II chronically at low dose. After reconstruction of a stenosed renal artery, or excision of a post-stenotic kidney, the angiotensin II/blood pressure relationship returns slowly to normal. In this second phase of one-clip, two-kidney hypertension, the long-term administration of saralasin, or of converting enzyme inhibitor, can also return arterial pressure to normal; brief administration of these drugs is less effective or ineffective. The results are compatible with, although they do not conclusively establish, an important slow pressor action of the renin-angiotensin system in the second phase of one-clip, two-kidney hypertension. This provides a rational basis for the use of captopril clinically in this condition.

Topics: Adult; Angiotensin I; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Captopril; Dogs; Female; Furosemide; Humans; Hypertension, Renal; Male; Middle Aged; Potassium; Proline; Radioimmunoassay; Rats; Renal Artery Obstruction; Renin; Saralasin; Sodium

Topics: Adenoma; Adrenal Cortex Neoplasms; Aldosterone; Angiotensin I; Angiotensin II; Female; Humans; Hyperaldosteronism; Hypertension; Hypertension, Renal; Kidney Neoplasms; Pregnancy; Pregnancy Complications, Cardiovascular; Renal Artery Obstruction; Renal Dialysis; Renin; Sodium

Angiotensin-(1-7) modulates renal blood flow in humans with essential hypertension by inducing vasodilation and counterbalancing angiotensin II-induced vasoconstriction. Little is, however, known about the effects of angiotensin-(1-7) in kidneys with atherosclerotic renal artery stenosis. We previously demonstrated that the effect of angiotensin-(1-7) is reduced in patients with increased activity of the renin-angiotensin system. As the renin-angiotensin system is also activated in kidneys with renal artery stenosis, we hypothesized that the vasodilatory effect of angiotensin-(1-7) is also reduced in such kidneys.. Therefore, we selectively measured mean renal blood flow (¹³³Xenon washout method) before and during local infusion of angiotensin-(1-7) (0.27, 0.9, and 2.7 ng/kg per min) in hypertensive patients who were angiographically evaluated for the presence of renovascular abnormalities. Data were analyzed in three groups: stenotic kidneys, nonstenotic kidneys with renal artery stenosis of the contralateral kidney (contralateral stenotic kidneys), or essentially hypertensive controls without renovascular abnormalities (matched for urinary sodium excretion).. Angiotensin-(1-7) infusion resulted in an increase in renal blood flow in matched controls. In stenotic kidneys however, the effect of angiotensin-(1-7) was significantly reduced as compared to controls. The angiotensin-(1-7) effect in contralateral stenotic kidneys was comparable to controls.. Angiotensin-(1-7)-induced vasodilation is reduced in stenotic kidneys, but not in contralateral stenotic kidneys. This suggests that the altered blood flow regulation in kidneys with atherosclerotic renal artery stenosis is a local phenomenon and not related to generalized atherosclerotic burden. Probably, the renin-angiotensin system activation, bioavailability of nitric oxide, and structural changes in the stenotic kidney play a role in this phenomenon.

Topics: Angiotensin I; Case-Control Studies; Essential Hypertension; Female; Humans; Hypertension; Kidney; Male; Middle Aged; Peptide Fragments; Renal Artery; Renal Artery Obstruction; Renal Circulation; Renin-Angiotensin System; Vasodilation

Chymase degrades angiotensin I (AI) to form angiotensin II (AII), probably constituting a bypass of the renin-angiotensin cascade. Chymase activity increases in some vascular diseases. In the kidney, an increase in chymase activity was reported in an animal model of ischemic kidney of renovascular hypertension (RVH); however, no such evidence has been provided in humans. We treated a 64-year-old patient with severe unilateral RVH and atherosclerosis, for whom removal of the ischemic kidney was the only option. Using immunohistochemical staining, we investigated chymase activity in the removed kidney and associated artery and vein. An increase in chymase activity, together with mast cells infiltrating the interstitium, was observed where interstitial fibrosis was seen. In the renal artery, where severe atherosclerosis was seen, and also in the vein, mast cell infiltration in the adventitia was accompanied by chymase. The captopril test showed an increase in serum aldosterone level, with a concomitant increase in plasma renin activity and decrease in blood pressure. Because the decrease in blood pressure implies a decrease in circulatory AII levels, it is plausible that in this patient, chymase had a role in AII formation in the adrenal gland to stimulate aldosterone secretion. Thus, by means of captopril, AI levels increased, and chymase may have produced AII in loci tissues, which, in turn, stimulated aldosterone secretion. This is the first report of an increase in chymase activity in the interstitium of an ischemic kidney and renal artery and vein in a patient with RVH and atherosclerosis.

Topics: Angiography, Digital Subtraction; Angiotensin I; Angiotensin II; Arteriosclerosis; Captopril; Chymases; Female; Humans; Hyperaldosteronism; Hypertension, Renovascular; Ischemia; Kidney; Mast Cells; Middle Aged; Nephrectomy; Renal Artery; Renal Artery Obstruction; Renal Veins; Renin; Renin-Angiotensin System; Serine Endopeptidases; Smoking

The diagnostic utility of post-captopril renal vein renin (RVR) measurements was quantitated in 43 patients (mean age 62, range 41 to 77 years) undergoing aortography to rule out renovascular hypertension (RVHT), and then compared with that of pre-captopril RVR measurements. Four patterns of post-captopril RVR secretion were defined: 1) unilateral hypersecretion (stenotic/peripheral [S/P] > 2.0) and contralateral suppression (C/P) (< 1.25) (n = 12); 2) bilateral hypersecretion (S/P > 2.0, C/P > 1.25) (n = 14); 3) bilateral suppression (peripheral plasma renin activity [PRA] < 1.0 ng/mL/h) (n = 12); and 4) "normal" (RVR/PRA < 2.0 bilaterally) (n = 5). Using the radiologic findings as the definitive test, the sensitivity and specificity of post-captopril RVR measurements in detecting unilateral or bilateral renal artery stenoses (85% or greater of lumen) was 61 and 96%, and 92 and 90%, respectively, a significant improvement compared with those of pre-captopril RVR measurements (44 and 62%, and 17 and 93%, respectively). Post-captopril RVR measurements facilitated the diagnosis of both hypersecretion and, when present, contralateral suppression of renin, and therefore, are useful in the diagnosis of atherosclerotic RVHT, and in planning its treatment. However, confirmation by more extensive prospective studies, including treatment outcome, is needed.

Topics: Adult; Aged; Angiotensin I; Aortography; Arteriosclerosis; Captopril; Female; Humans; Hypertension, Renovascular; Iodine Radioisotopes; Male; Middle Aged; Radioimmunoassay; Renal Artery Obstruction; Renal Veins; Renin

To study regional metabolism and production of angiotensin II, we measured steady-state plasma levels of 125I-angiotensin I and II and endogenous angiotensin I and II in the aorta and the antecubital, femoral, renal, and hepatic veins during systemic infusion of 125I-angiotensin I or II. Extraction of arterially delivered angiotensin II ranged from 30-50% in the limbs to 80-100% in the renal and hepatomesenteric vascular beds both in essential hypertension (n = 13) and in unilateral renal artery stenosis (n = 7). Across the limbs, 20-30% of arterially delivered angiotensin I was converted to angiotensin II in both groups, and there was no arteriovenous gradient in endogenous angiotensin II. No conversion of arterially delivered angiotensin I was detected across the renal and hepatomesenteric beds, and there was net extraction of angiotensin II from the systemic circulation by these beds. Although regional production of angiotensin I at tissue sites made a significant contribution to its level in the veins, little of this locally produced angiotensin I reached the regional veins in the form of angiotensin II, even in the kidney with artery stenosis, where the venous levels of locally produced angiotensin I were particularly high. These results provide no evidence for a source of circulating angiotensin II other than blood-borne angiotensin I and illustrate the high degree of compartmentalization of angiotensin I and II production.

Topics: Adult; Angiotensin I; Angiotensin II; Arteries; Blood Pressure; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged; Renal Artery Obstruction; Tissue Distribution; Veins

To estimate the renal extraction and de novo production of angiotensin I and to assess the contribution of blood-borne renin to renal angiotensin I production, the aortic and renal venous plasma levels of renin and intact [125I]angiotensin I and endogenous angiotensin I during continuous systemic intravenous infusion of monoiodinated [125I]angiotensin I were measured in subjects with unilateral renal artery stenosis (n = 8) who were treated with captopril (50 mg b.i.d.). Results demonstrated that 80% of angiotensin I delivered by the renal artery was extracted both by the affected and the unaffected kidney and that on both sides a major part of angiotensin I in the renal vein was derived from intrarenal de novo production. Production of plasma angiotensin I was in excess over extraction (p less than 0.01) on the affected side, whereas extraction was in excess over production (p less than 0.01) on the contralateral side. The plasma level of de novo intrarenally produced angiotensin I in the renal vein was seven times higher on the affected side than the contralateral side. This difference was by far too big to be explained by a difference in the transit time of blood between the two kidneys, by an augmented production of angiotensin I in the circulating blood passing through the affected kidney due to the higher level of venous plasma renin activity in that kidney, or by the combination of both.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Angiotensin I; Angiotensin II; Chromatography, High Pressure Liquid; Female; Humans; Kidney; Male; Middle Aged; Renal Artery Obstruction; Renin

The converting enzyme inhibitor enalapril, in single daily doses of 10 to 40 mg, was given to 20 hypertensive patients with renal artery stenosis. The decrease in blood pressure six hours after the first dose of enalapril was significantly related to the pretreatment plasma concentrations of active renin and angiotensin II, and to the concurrent decrease in angiotensin II. Blood pressure decreased further with continued treatment; the long-term decrease was not significantly related to pretreatment plasma renin or angiotensin II levels. At three months, 24 hours after the last dose of enalapril, blood pressure, plasma angiotensin II, and converting enzyme activity remained low, and active renin and angiotensin I high; six hours after dosing, angiotensin II had, however, decreased further. The increase in active renin during long-term treatment was proportionately greater than the increase in angiotensin I; this probably reflects the diminution in renin substrate that occurs with converting enzyme inhibition. Long-term enalapril treatment increased renin secretion by more than 10-fold, and renal venous and peripheral plasma renin concentration by more than 20-fold; however, the mean renal venous renin ratio was not changed. Enalapril caused a reduction in effective renal plasma flow via the affected kidney but a marked and consistent increase on the contralateral side, where renal vascular resistance decreased. The overall increase in effective renal plasma flow was significantly related to the decrease in angiotensin II. Overall glomerular filtration rate was lowered, and serum creatinine and urea increased. Enalapril alone caused a long-term reduction in exchangeable sodium, with slight but distinct increases in serum potassium. In five patients with bilateral renal artery lesions, enalapril given alone for three months did not cause renal function to deteriorate. Enalapril was well tolerated and provided effective long-term control of hypertension; only two of the 20 patients studied required concomitant diuretic treatment.

Topics: Administration, Oral; Adult; Aldosterone; Angiotensin I; Angiotensin II; Blood Pressure; Body Composition; Creatinine; Dipeptides; Drug Evaluation; Enalapril; Female; Heart Rate; Humans; Hypertension; Kidney; Male; Middle Aged; Posture; Potassium; Renal Artery Obstruction; Renin; Sodium

The spontaneous variations in renal vein renin activity (RVRA) and in peripheral vein renin activity (PVRA) were studied in one normotensive and nine hypertensive patients. Eight of the hypertensive patients had renal artery stenosis on one or both sides. Blood samples were drawn simultaneously from the two renal veins and from a peripheral vein every fifth or tenth minute for one hour. Plasma renin activity (PRA) was measured by radioimmunoassay. The precision of the PRA assay, expressed as coefficient of variation, was related to the PRA level. A large intra-individual variations was found in RVRA, the RVRA ratio and PVRA even in patients with unilateral renovascular hypertension. The intra-individual variation could not be explained by specimen collection error or by error of the assay procedure. The variation seems to be reflect a biological fluctuation. The clinical implication of these findings is that repeated, simultaneous collection from the two renal veins, avoidance of factors known to decrease renin secretion. and consideration of the relation between the RVRA ratio and RVRA level are of importance in the preoperative evaluation of patients with renal artery stenosis.

Topics: Adult; Angiotensin I; False Positive Reactions; Female; Humans; Hypertension, Renal; Hypertension, Renovascular; Male; Methods; Middle Aged; Renal Artery Obstruction; Renal Veins; Renin

Malignant hypertension with severe hyponatraemia, hypokalaemia, depletion of sodium and potassium, and elevated blood levels of renin, angiotensin I, angiotensin II, aldosterone, and arginine vasopressin developed in a woman with renal-artery occlusion. Plasma angiotensin II was disproportionately high in relation to exchangeable sodium. Captopril, by inhibiting conversion of angiotensin I to angiotensin II, further elevated the blood levels of renin and angiotensin I but corrected all other abnormalities. Unilateral nephrectomy was subsequently curative.

Topics: Aldosterone; Angiotensin I; Angiotensin II; Arginine Vasopressin; Blood Pressure; Captopril; Female; Humans; Hypertension, Malignant; Hyponatremia; Middle Aged; Potassium; Proline; Renal Artery Obstruction; Renin; Syndrome

Topics: Adolescent; Adult; Aldosterone; Angiotensin I; Angiotensin II; Angiotensins; Blood Pressure; Captopril; Female; Humans; Hypertension; Male; Middle Aged; Potassium; Proline; Renal Artery Obstruction; Renin; Sodium

Topics: Adolescent; Adult; Angiotensin I; Angiotensin II; Angiotensins; Humans; Hypertension; Middle Aged; Renal Artery; Renal Artery Obstruction; Renal Veins; Renin