Renography with captopril. Changes in a patient with hypertension and unilateral renal artery stenosis.

In a 56-year-old man with severe familial hypertension and unilateral renal artery stenosis, captopril induced striking changes in the renograms of the affected kidney. After injection of orthoiodohippurate sodium I 131, the uptake phase was unchanged but the later curve showed continuous accumulation. In contrast, the uptake of technetium Tc 99m diethylenetriamine pentracetic acid was abolished. These changes are compatible with a cessation of filtration and maintenance of renal blood flow. After balloon dilatation of the stenosis, the blood pressure became lower, and these changes could no longer be demonstrated. The captopril renogram may provide useful information on the dependency of hypertension on unilateral renal artery stenosis.

Blood and extracellular fluid volume in patients with Bartter's syndrome.

Blood and extracellular fluid volumes were measured in four adult patients with Bartter's syndrome and compared with those of 21 healthy control subjects. Extracellular fluid volumes were significantly lower than in the control group (-7%), whereas blood volumes were within the normal range. Consequently, the ratio of blood volume to interstitial fluid volume was significantly elevated (0.42 v normal 0.35). The results are consistent with the concept that a tubular reabsorption defect is present in Bartter's syndrome.

Renovascular hypertension identified by captopril-induced changes in the renogram.

Radioisotope renography was performed in 21 patients with hypertension and unilateral renal artery stenosis with and without premedication with 25 mg of captopril, and the results were compared with the effect of percutaneous transluminal angioplasty on the blood pressure, assessed 6 weeks after angioplasty. Angioplasty caused a considerable decrease in blood pressure in 15 of the 21 patients. In 12 of these 15 patients, captopril induced changes in the time-activity curves of the affected kidney only, suggesting deterioration of the excretory function of that kidney, while the function of the contralateral kidney remained normal. After angioplasty the asymmetry in the time-activity curves diminished despite identical pretreatment with captopril. Such captopril-induced unilateral impairment of the renal function was not seen in the six patients with unilateral renal artery stenosis whose blood pressure did not change after percutaneous transluminal angioplasty or in 13 patients with hypertension and normal renal arteries. The functional impairment of the affected kidneys was characterized by a decrease of 99mTc-diethylenetriamine pentaacetic acid uptake and a delay of 131I-hippurate excretion, while the 131I-hippurate uptake remained unaffected. These data are in agreement with a reduced glomerular filtration rate and diuresis during preservation of the renal blood flow, changes that can be expected after converting enzyme inhibition in a kidney with low perfusion and an active, renin-mediated autoregulation of the glomerular filtration rate. These data suggest that functional captopril-induced unilateral changes, shown by split renal function studies with noninvasive gamma camera scintigraphy, can be used as a diagnostic test for renovascular hypertension caused by unilateral renal artery stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Atenolol and chlorthalidone on blood pressure, heart rate, and plasma renin activity in hypertension.

The antihypertensive effect of atenolol, with and without chlorthalidone, on hypertension was assessed in an outpatient as well as in an inpatient study. In the outpatient study atenolol alone induced decreases in systolic and diastolic BP amounting to 20 and 15 mm Hg. Maximal response of BP and HR developed within a week at the lowest dose used (100 mg twice daily). Combined atenolol-chlorthalidone treatment decreased lying and standing systolic BP by 7 and 14 mm Hg more than atenolol alone, but diastolic BP was decreased little more. In the inpatient study the addition of atenolol to chlorthalidone therapy in a dose of 100 mg twice daily resulted in a maximal decrease in BP within 3 days. At this dose PRA was lowered only slightly. Larger doses did not lead to any significant further decrease in BP, whereas PRA fell progressively. Our results indicate that, in contrast to nonselective blockade, specific beta-1-adrenoceptor blockade by atenolol is capable of inducing a distinct antihypertensive effect, unrelated to suppression of PRA. The decrease in PRA after larger doses of atenolol was not accompanied by a further decrease in BP. Because diuretic-induced renin release plays a role in the maintenance of the BP, our findings suggest that at higher dosages a hypertensive effect of the beta blocker compensated for the hypotensive effect of the decrease in PRA.

Effects of atenolol and propranolol when added to long-term antihypertensive diuretic therapy.

The antihypertensive effects of atenolol and propranolol were compared in a double-blind crossover study of 19 patients with essential hypertension (World Health Organization, I and II) who were receiving long-term diuretic treatment (chlorthalidone, 50 mg daily) during the study. After a 3-wk placebo period, a beta-adrenergic antagonist was administered once daily (atenolol, 50 mg daily, or propranolol, 80 mg daily) for a week. If the MAP was more than 108 mm Hg at the end of the week, dosage of the beta-blocker was doubled the following week; when necessary, doubling was repeated to a maximum dose of 640 mg propranolol and 400 mg atenolol daily. Fifty milligrams atenolol had a greater effect than 80 mg propranolol and was as effective as 160 mg propranolol. The dose-response curve flattened off after 160 mg propranolol and 50 mg atenolol daily. The two highest doses of atenolol lowered MAP more than the highest doses of propranolo. Heart rate slowing was the same for both drugs and did not correlate with the fall in blood pressure. PRA was suppressed by all doses of propranolol, whereas atenolol suppressed PRA only at the 2 highest doses, (200 and 400 mg daily). With the lower propranolol doses, the percent MAP change correlated weakly with the percent PRA change (80 mg--r = 0.41, p less than 0.1; 160 mg--r = 0.64, p less than 0.05). Side effects were minimal, and were noted only with 640 mg propranolol; with this exception, the percentage of patients with no complaints rose when placebo was replaced by beta-blockers.

One and three doses of propranolol a day in hypertension.

In 26 patients with essential hypertension who were on continuous chlorthalidone therapy, 1 and 3 daily doses of propranolol were compared in a crossover study. Plasma propranolol levels and heart rates had larger daily fluctuations on single-dose therapy than on 3 times daily; plasma renin activity was more constant. There was no significant difference in blood pressures. Once-daily propranolol dosage was well tolerated and possibly gave less rise to the troublesome side effect of vivid dreaming.

Changes in blood pressure and body fluid volumes during diuretic therapy in patients with essential hypertension who receive enalapril.

We evaluated the effect of additional chlorthalidone therapy on blood pressure and body fluid volumes in 10 patients with essential hypertension who did not respond to chronic converting enzyme inhibition with enalapril. Values assessed after 3 days and 6 weeks of combined enalapril and chlorthalidone therapy were compared with initial values during enalapril monotherapy. After 3 days the mean arterial pressure (MAP), plasma volume (PV), blood volume (BV), and extracellular fluid volume (ECFV) decreased. There was a positive correlation between the percentage decreases in MAP and BV. After 6 weeks the MAP decreased further, but the decreases in PV, BV, and ECFV were less pronounced. At this time there was a positive correlation between the percentage decreases in MAP and ECFV. Our results support the hypothesis that contraction of the ECFV is an antihypertensive mechanism of diuretics. The antihypertensive effect of diuretics is enhanced during converting enzyme inhibition, while the body remains protected against volume deficits, possibly by the lower blood pressure itself.

Captopril renography and the effect of percutaneous transluminal angioplasty on blood pressure in 94 patients with renal artery stenosis.

We treated 94 patients by percutaneous transluminal angioplasty (PTA) for renal artery stenosis (RAS). Prior to PTA, a renogram during angiotensin converting enzyme (ACE) inhibition with captopril was performed, but the result did not influence the decision to treat. The parenchymal time activity curves were judged by visual interpretation. Of the 94 patients, 51 had unilateral and 43 bilateral RAS. In 17 patients with bilateral RAS, PTA could be performed only in the least affected kidney; because of this the effect of PTA on their blood pressure could not be evaluated. Of the remaining 77 patients, a positive captopril renogram was seen in all 31 cured patients, in 22 of the 27 patients with improvement, and in six of the 19 patients with no change of their blood pressure. The sensitivity of the tests for cure and improvement of the blood pressure was 91% (53/58 patients) for all patients, 95% in patients with unilateral RAS (35/37), and 86% (18/21 patients) in patients with bilateral RAS, bilaterally treated. In 18 patients with a negative captopril renogram the blood pressure improved in five, and did not change in 13 patients. The success of PTA in patients with a negative captopril renogram was so poor that we feel it would have been better not to have performed angiography and PTA at all. In conclusion, captopril renography is a useful investigation in assessing the likelihood of blood pressure reduction after PTA of renal artery stenosis.

Renovascular hypertension and renal insufficiency treated with left nephrectomy and right autotransplantation.

A patient presented with renal failure and severe hypertension. Arteriography showed a non-functioning kidney due to occlusion of the renal artery. The artery of the other contralateral kidney seemed unaffected. Converting enzyme inhibition resulted in normalization of the blood pressure, but this was accompanied by worsening of the renal failure. This was the clue for the detection of an origostenosis of the artery of the contralateral kidney, which could only be diagnosed by oblique angiograms. A revascularisation procedure by renal autotransplantation was performed. Simultaneously the non-functioning kidney was excised. The procedure resulted in an uneventful recovery of renal function. Diagnostic and therapeutic issues are discussed.

[Results of percutaneous transluminal angioplasty in renal artery stenosis during the period 1978-1986]. / Resultaten van percutane transluminale angioplastiek bij nierarteriestenosen in de periode 1978-1986.

UNLABELLED: Two hundred and thirteen patients with hypertension and renal artery stenosis were treated with percutaneous transluminal renal angioplasty (PTRA). The angiographic appearance was typical of atherosclerosis in 134 patients and of fibromuscular dysplasia (FMD) in 52 patients, and could not reliably be classified in one of these groups in 27. In these patients 272 renal artery stenoses were treated. In 81% of these patients the PTRA was technically successful. The antihypertensive result in this group of 210 patients was positive (cure or improvement) in 80%. The life-table results after 5 years show cure or improvement in the atherosclerotic group (n = 35) in 80.27%, in the FMD group (n = 20) in 88.83% and in the unclassified group (n = 10) in 74.27%. One patient died from a mesenteric thrombosis and one from a myocardial infarction which both occurred within a few days after PTRA. Accordingly, the mortality was less than 1%. IN CONCLUSION: PTRA appears to be a good treatment of renovascular hypertension caused by atherosclerosis or FMD, with good long-term antihypertensive effects.

Apparently high plasma angiotensin II levels in patients with essential hypertension treated by converting enzyme inhibition.

Plasma angiotensin I and II (AI and AII) were measured in 13 patients with essential hypertension before and during chronic treatment with enalapril (MK 421) and in seven subjects during an acute study. Two techniques were used for simultaneous extraction of AI and AII. Despite appropriate correction for cross-reaction of AI with the AII antibody, one of the techniques gave consistently higher AII and lower AI levels in plasma of subjects treated with enalapril. The possibility of in vitro conversion of AI into AII-immunoreactive material during the purification or the radioimmunoassay steps should be considered. The use of the alternative technique is proposed for simultaneous processing of blood samples for AI and AII.

Clonidine withdrawal. Mechanism and frequency of rebound hypertension.

1. The frequency and pathophysiology of the clonidine withdrawal syndrome was studied in fourteen hypertensive patients on chronic clonidine therapy. 2. After sudden cessation of clonidine (900 microgram daily) almost all of the patients showed an excessive increase of the heart rate and blood pressure. Seven of the fourteen patients had subjective symptoms, in three severe enough to require interruption of observation by therapeutic intervention 12 to 60 h after the last dose of clonidine. After clonidine withdrawal, NAE increased to abnormally high values in correlation with the blood pressure (P less than 0.01) and heart rate (P less than 0.001), whereas PRA even decreased initially, probably secondary to the rise of the blood pressure, and only rose, although not significantly, 48 h after withdrawal. PRA was not correlated with NAE, heart rate, or blood pressure. 3. It is concluded that the clonidine withdrawal phenomenon is a frequently occurring and potentially dangerous syndrome. Overactivity of the sympathetic nervous system is mainly responsible, without the mediation of the renin angiotensin system. This also explains our experience that adrenergic beta-receptor blocking drugs do not prevent the rise in BP, although they alleviate some of the symptoms.

Sodium intake and the effects of isoproterenol and exercise on plasma renin in man.

Changes in heart rate, blood pressure, and plasma renin activity (PRA) were assessed during infusion of increasing doses of isoproterenol and during increasing work loads of dynamic exercise in five normal young men. Studies were performed at three levels of dietary sodium restriction: normal, moderately, and more severely restricted. Isoproterenol induced the expected dose-related increases in heart rate, systolic blood pressure, and PRA and decreases in diastolic blood pressure. Changes in dietary sodium intake affected these changes only to a minor degree. Dynamic exercise also induced the expected work-load-related increases in heart rate, systolic blood pressure, and PRA and decreases in diastolic blood pressure. Also these changes were not significantly affected by changes in dietary sodium intake. Apparently dietary sodium restriction does not sensitize the renin-releasing mechanisms to sympathetic stimulation.