Blood pressure response to percutaneous transluminal angioplasty for renovascular hypertension: an overview of published series.

OBJECTIVE--To evaluate the efficacy and safety of transluminal angioplasty in the treatment of renovascular hypertension. DESIGN--Overview of 10 published case series. SETTING--Mostly tertiary referral centres. PATIENTS--691 Patients treated by angioplasty for renovascular hypertension, 464 for atherosclerotic stenosis, 193 for fibromuscular stenosis, and the remainder mainly for post-transplant stenosis. The inclusion criteria varied considerably between studies. INTERVENTIONS--Percutaneous transluminal renal artery angioplasty (successful or attempted); prophylaxis against restenosis in most cases. Policies on antihypertensive drug treatment and follow up varied. MAIN OUTCOME MEASURES--Blood pressure response as defined in the individual papers, with each patient classified as either cured, improved, or failed. Each study used a different definition of improvement in blood pressure. Complication rates. RESULTS--Follow up data were available for 670 patients. The procedure was technically successful in 611 patients (88%). The overall cure rate for hypertension was 24% (163 patients) and a further 43% (286) were "improved." There were large and significant variations between studies in the rate of technical success and also the blood pressure outcome. In each series patients with fibromuscular lesions, had a higher cure rate than those with atherosclerotic lesions (overall cure 50% v 19% odds ratio 3.9, 95% confidence interval 2.6 to 6.0). Complications were reported in 63 (9%) patients and three patients died (0.4%). CONCLUSIONS--The evidence for the value of angioplasty in treating renovascular hypertension has serious limitations. Angioplasty for fibromuscular disease seems to be worth while, but for atherosclerotic lesions the benefit appears to be small and its efficacy needs to be compared with medical therapy in randomised trials. These findings emphasise the importance of early formal evaluation of new therapeutic techniques.     

Apport de la scintigraphie rénale avec test au captopril dans l’exploration de l’hypertension artérielle rénovasculaire : à propos d’un cas

IntroductionDynamic renal scintigraphy with ^99mTc-DTPA and captopril test is a non-invasive functional method for the diagnosis of renovascular hypertension. It allows differentiating between hypertension induced by renal arterial stenosis from primary arterial hypertension with an incidental stenosis.Case reportA 14-year-old girl, without previous medical history, developed a severe arterial hypertension with cephalgias and ears buzzing. Auscultation revealed a murmur in the left lumbar pit. Renal angiography objectified a stenosis of the infrarenal aorta due to a circumferential parietal thickening associated to renal arteries stenosis more marked in the left side. Dynamic renal scintigraphy after administration of captopril highlighted a marked collapse of the rate of tracer uptake exceeding 40% on the left side with an increase in the time of collecting on the right side testifying a frankly positive test prevailing on the left. A transluminal angioplasty of the left renal artery and a revascularisation surgery on the right side were carried out. The evolution was marked by an improvement of blood pressure figures.DiscussionDynamic renal scintigraphy using ^99mTc-DTPA with captopril test constitutes a non-invasive process with a low dosimetry for the patients. Its principal goal is to affirm the role of renovascular stenosis in the origin of arterial hypertension and to determine which hypertensive patients with renal arterial stenosis can be treated successfully by surgical or endoscopic revascularisation of the kidney.     

Renal vein plasma adenosine 3',5'-cyclic monophosphate in renovascular hypertension.

The concentration of plasma adenosine 3'',5''-cyclic monophosphate (cyclic AMP) and plasma renin activity (PRA) were measured concomitantly in blood from both renal veins and in arterial blood in 22 hypertensive patients. In the nine patients with true renovascular hypertension the concentration of plasma cyclic AMP was greater in the venous effluent of the kidney affected by the renal artery stenosis than in that of the unaffected or less affected kidney. The arteriovenous difference in cyclic AMP concentration was less on the affected side in all but one patient. The arteriovenous differences in PRA identified the affected kidney as the source of hyper-reninemia and showed that renin release from the other kidney was suppressed. In the 13 patients with hypertension associated with but unrelated to renal artery stenosis there were no consistent patterns of cyclic AMP concentration or PRA in the venous effluent of the kidneys or of their arteriovenous differences. In renovascular hypertension the venous effluent of the kidney affected by renal artery stenosis contains not only more renin but also more cyclic AMP, owing to either increased cyclic AMP production or decreased excretion or extraction of cyclic AMP by the affected kidney. This unilateral increase in cyclic AMP concentration may become a complementary diagnostic feature of true renovascular hypertension.     

Plasma atrial natriuretic factor concentrations in essential and renovascular hypertension.

Plasma atrial natriuretic factor concentrations were measured in 44 patients with mild untreated essential hypertension and 48 normotensive controls. Mean venous plasma atrial natriuretic factor concentrations were 13.2 (SEM 1.5) and 13.0 (1.3) ng/l in the hypertensive patients and controls, respectively. Plasma atrial natriuretic factor concentrations were significantly correlated with age in both groups. Plasma atrial natriuretic factor concentrations were also measured during renal vein catheterisation in a group of 15 hypertensive patients; of these, eight had renovascular hypertension, and in all eight cases plasma atrial natriuretic factor concentrations were increased in the aorta and inferior vena cava. It is concluded that mild essential hypertension is not associated with increased plasma atrial natriuretic factor concentrations, whereas an age related increase in concentrations occurs in hypertensive and normotensive people.     

The role and rationale of nuclear medicine procedures in the differential diagnosis of renovascular hypertension

The use of radionuclides in the differential diagnosis of renovascular hypertension has gone through many periods of enthusiasm and of disappointment. Regardless of the problems with the routine renogram, the availability of gamma camera renal evaluation makes possible meaningful preintervention of screening. The use of the test as a follow-up procedure is an extremely important but often overlooked application of radionuclides in the evaluation of renovascular hypertension. The radionuclide technique is a sensitive and accurate method of evaluating the results of percutaneous angioplasty or surgery or renal function in the affected kidney of patients with renovascular disease.A major change in our approach to the nuclear medicine diagnosis of renovascular hypertension has been the introduction of captopril renography. Although there is still a great deal of work to be done and many investigators are actively studying captopril renography, the potential of the test is clear. Captopril renography should include a baseline renogram, followed by the administration of 25 mg of captopril and a repeat study.Specificity and sensitivity data on this test probably will not be available for several years, but preliminary results are encouraging enough to justify routine use at this time in clinics in which screening for renovascular hypertension is carried out.     

Effects of phospholipid platelet activation factor on proliferation of B-lymphocytes of the peripheral blood of healthy donors and patients with bronchial asthma

The influence of the phospholipid platelet activation factor (PAF) was studied on pokeweed mitogen (PWM)-stimulated proliferation of peripheral blood lymphocytes in patients with bronchial asthma and normal subjects. It was found that PAF exerts dose-dependent activation with following suppression mainly on B-cells after its action on the whole population of lymphocytes activated by PWM. Besides, the influence of PAF on lymphocyte proliferation seemed to be mediated by monocytes since removal of monocytes from the whole population of mononuclear cells abolished the lymphocyte activation induced by PWM. Indomethacin inhibits lymphocyte proliferation activation induced by PAF. The results indicate that PAF has an effect on the IgE and IgG synthesis by blood B-lymphocytes in patients with bronchial asthma.     

Follow up study of 70 patients with renal artery stenosis treated by percutaneous transluminal dilatation.

Between April 1978 and April 1981, 70 patients with hypertension and renal artery stenosis were treated by percutaneous transluminal arterial dilatation. Selection of the patients was based solely on arteriographic criteria. Arteriography after dilatation showed considerable widening of the stenosed area in all patients. In 65 patients the effect of treatment on the blood pressure was assessed during follow up periods of one to four years. In 14 of these patients the hypertension was cured, in 29 it was improved, and in 22 there was no change. Patients with fibromuscular lesions benefited distinctly more than did those with atheromatous stenosis, only one of the 21 patients with fibromuscular lesions showing no change as compared with 21 of the 44 patients with atheromatous lesions. The only serious complication encountered was microcholesterol emboli, which developed in two patients with severe atheromatous lesions of the aorta. In the atheromatous group age and overall renal function had no influence on the blood pressure response. In the subgroup of patients with a unilateral lesion the renal vein renin ratios and asymmetrical curves obtained by renography had only a very limited predictive value. In experienced hands percutaneous transluminal arterial dilatation is relatively safe, and this study suggests that it should be attempted in all patients with renal artery stenosis. Only in patients with severe atheromatosis of the aorta should the risk associated with the catheterisation be weighed against the 50% or so chance of benefit from the procedure.     

Increase in plasma digitalis-like activity during percutaneous transluminal coronary angioplasty in patients with coronary stenosis

Despite the fact that numerous studies have been published regarding the possible presence in plasma of an endogenous Na-K pump inhibitor with a digitalis-like structure in essential hypertension, very little is known about this factor in heart disease in general, and in situations characterized by low cardiac output. We measured the ability of plasma obtained from the femoral vein to inhibit a human renal Na(+)-K+ ATPase before and immediately after percutaneous transluminal coronary angioplasty (PTCA) in 6 patients suffering from angina pectoris and severe coronary stenosis. Intraerythrocyte sodium and potassium concentrations were also measured simultaneously. Na(+)-K+ ATPase inhibition proved significantly greater after angioplasty as compared to basal activity (percentage inhibition: 31.5 +/- 7.8 vs 16.1 +/- 12.2). No significant changes in intraerythrocyte sodium and potassium were detected. Though we are not in a position to define the mechanism underlying the increase in the digitalis-like factor, a plausible hypothesis may be that the reduction in cardiac output during PTCA by raising cardiac pressures may stimulate the production of a factor of compensatory inotropic significance.     

The role of the thrombocyte-activating factor in the development of circulatory disorders in the postischemic shock reaction

Experiments carried out on anesthetized dogs have shown that reperfusion of long-ischemized leg tissues is accompanied by a significant decrease of the cardiac output and myocardial contractility. Restriction of the venous return to the heart is important in the cardiac output decrease due to an increase of venous compliance and blood pooling on the peripheral circulation. The preliminary blockade of platelet-activating factor (PAF) receptors decreases degree of the cardio- and hemodynamic disturbances after reperfusion of ischemized tissues and prevents development of pulmonary hypertension. Similarity of the postreperfusion central and peripheral hemodynamic disturbances and animal responses to injection of the exogenous PAF as well as the presence of the protective effect of PAF-receptor antagonist BNo. 52021 permit concluding, that PAF takes part in the development of postischemic shock reaction and its receptor blockade can be used to prevent postreperfusion hemodynamic disorders.     

Synthesis and release of platelet-activating factor by stimulated human mononuclear phagocytes

Platelet-activating factor (PAF) is a potent phospholipid mediator that may participate in inflammatory responses by virtue of its ability to activate platelets, leukocytes, and vascular cells. We examined the synthesis and release of PAF by human peripheral blood monocytes (PBM) isolated by countercurrent elutriation. PAF was produced after stimulation by calcium ionophore A23187 (IoA), opsonized zymosan (OpsZ), and PMA with a relative order of potency IoA much greater than OpsZ greater than PMA. The portion of PAF subsequently released from the cell was dependent on the specific agonist, the time of incubation, and the presence of albumin. Under optimal conditions, PBM released 67, 49 and 32% of the total PAF produced in response to IoA, OpsZ, and PMA, respectively. Changes in PAF metabolism were observed in PBM that were examined after short term adherence or differentiation into macrophages. Adherent PBM accumulated and released less PAF than suspended monocytes, and monocyte-derived macrophages produced less PAF than the parent PBM. The ability of monocytes to release significant amounts of newly synthesized PAF from the cell is unusual among human cell types, which in general retain the vast majority of the lipid, and may be of particular pathophysiologic importance.     

Reconstructive vascular surgery for renovascular hypertension

Forty-six patients who underwent renal artery repair for presumptive renovascular hypertension are presented. Preoperative investigation included a rapid sequence IVP, a high quality angiogram and split function studies, as well as renin assays of renal venous blood in the more recent cases. Atherosclerosis was the causative pathological lesion in 60% of the patients, with fibromuscular dysplasia or miscellaneous causes of stenosis accounting for the remaining 40%.Surgical correction was usually obtained by bypass grafting (57%). Hypertension was cured or significantly improved in 36 patients (78%).Optimal results are dependent upon complete preoperative investigation and surgical repair of all the stenotic areas.     

Plasma Renin Activity and Angiotensin Pressor Dose in Hypertension: Correlation and Diagnostic Implications

Data obtained from 65 hypertensive patients showed a clear-cut positive correlation between peripheral plasma renin activity and the pressor response to exogenous angiotensin II (r =+0.75). For the various causes of hypertension, the mean values of plasma renin concentration were found to correspond closely to the mean values of the angiotensin pressor dose. In individual cases, however, the pressor dose of angiotensin was not found to be a reliable gauge of peripheral venous renin activity.It was impossible to establish a causal diagnosis from the results of the angiotensin infusion test or the renin level in peripheral blood under normal conditions. If, however, determinations are carried out on the renal venous effluent with sodium restriction and with the patient in the upright position the renin level is very valuable both in the diagnosis of renovascular hypertension and in predicting the probable outcome of surgical treatment.     

The intracellular retention of newly synthesized platelet-activating factor

The ether phospholipid platelet-activating factor (PAF) has been generally assumed to be released into the extracellular environment by the cells of origin, whereupon it effects its well-known mediator functions. However, during the generation of PAF by human neutrophils, it was noted that the majority of the measurable PAF remained associated with the cells. Accordingly, the intracellular and extracellular distribution of PAF was examined in neutrophils and several other cell types. No PAF was detected in association with unstimulated neutrophils. However, in stimulated neutrophils, PAF was produced and the majority of this material remained in association with the cells independent of the type of stimulus, dose of stimulus, or method of cell isolation used. This pattern of cell association of PAF was seen in all but one of the cell types tested. The retention of PAF by stimulated neutrophils was not due to spurious underestimates of the extracellular levels due to extracellular metabolism and inactivation of released PAF, nor to release followed by readsorption or binding of PAF to the cells. The retention of PAF also occurred in the presence of plasma and appears to be a common phenomenon. Thus, the majority of newly synthesized PAF appears to be retained within the cell and not released.     

The release of platelet-activating factor from human endothelial cells in culture

The release of platelet-activating factor (PAF) from stimulated human endothelial cells (HEC) cultured from normal term, umbilical cord veins is described. HEC in primary cultures released PAF after challenge with A23187, rabbit anti-human factor VIII (RaHu/FVIII), angiotensin II, and vasopressin. HEC subcultures maintained the ability to release PAF in the presence of A23187 and RaHu/FVIII, whereas the release of PAF in response to angiotensin II and vasopressin was not constant and was reduced. Control cultured, smooth muscle cells derived from umbilical cord veins, previously depleted of endothelial cells, did not release PAF under the above-mentioned stimulation. Plastic-adherent or cultured monocytes released PAF with A23187, but not with RaHu/FVIII, angiotensin II, and vasopressin. The release of PAF from HEC in primary cultures required the presence of extracellular cations and the activation of membrane phospholipase A2. PAF release induced by A23187, RaHu/FVIII, angiotensin II, and vasopressin was unaffected by indomethacin, an inhibitor of cyclooxygenase, which, however, favored the release of PAF from HEC stimulated with thrombin, a stimulus that did not affect HEC in the absence of indomethacin. PGI2 inhibited PAF release from stimulated HEC. The relevance of an acetylation process in the biosynthesis of PAF and HEC was supported by the following evidence: 1) the increase in PAF yield in the presence of sodium acetate and, particularly, of acetyl-CoA; 2) the incorporation of [14C]acetate into PAF molecules; 3) the loss of radioactivity and of biologic activity after treatment with phospholipase A2. These results indicate that HEC in culture are able to release PAF and that metabolic pathways similar to those described for leukocytes are involved.     

Failure of naloxone to influence surgical reversal of two-kidney, one-clip hypertension in the rat

The rapid fall in blood pressure after removal of the constricting clip in two-kidney one-clip (2K-1C) hypertension in the rat is not fully explained by inhibition of the renin-angiotensin system or change in sodium balance. It has been postulated that compounds released in the renal venous effluent following unclipping of 2K-1C rats have a central opiate-like action and endogenous opioids are recognized to have profound hypotensive properties. To investigate this, we removed the clip from, or performed a sham operation in, early phase (less than 6 weeks) 2K-1C hypertensive rats during an infusion of naloxone, an opioid antagonist, or vehicle alone. The infusion of naloxone did not affect the pattern of blood pressure fall in either unclipped or sham-operated rats. Both naloxone-treated and control groups were similarly normotensive at 24 hr postoperation, the MAP being significantly lower than in the sham-operated groups, which regained previously hypertensive levels. Heart rate was unchanged 24 hr postoperatively in all groups. Morphine-induced bradycardia and hypotension were significantly reduced by naloxone infusion. Thus, naloxone infusion had no effect on blood pressure or heart rate in either the sham-operated or the unclipped groups, indicating that endogenous opioids do not have a major role in the reversal of renovascular hypertension under these circumstances.     

Nocturnal blood pressure in normotensive subjects and those with white coat,primary, and secondary hypertension.

OBJECTIVE--To compare the mean nocturnal blood pressure of patients with various forms of renal and endocrine hypertension with that in patients with primary and white coat hypertension, and normal blood pressure. DESIGN--Ambulatory monitoring of blood pressure over 24 hours in a prospective study. SETTING--Two German centres for outpatients with hypertension and kidney diseases. SUBJECTS--176 normotensive subjects, 490 patients with primary hypertension including mild and severe forms, 42 with white coat hypertension, 208 patients with renal and renovascular hypertension, 43 with hypertension and endocrine disorders, and three with coarctation of the aorta. MAIN OUTCOME MEASURES--Fall in nocturnal blood pressure. RESULTS--Blood pressure in normotensive subjects fell by a mean of 14 mm Hg (11%) systolic and 13 mm Hg (17%) diastolic overnight (2200 to 0600). The falls in patients with primary and white coat hypertension were not significantly different. In all patients with renal and renovascular hypertension, however, the fall was significantly reduced (range of fall from 3/3 mm Hg to 7/9 mm Hg). In patients with hypertension and endocrine disorders the pattern of night time blood pressure was not uniform: patients with hyperthyroidism, primary hyperaldosteronism, and Cushing''s syndrome had significantly smaller reductions in blood pressure (6/8, 4/7, 3/6 mm Hg, respectively). In patients with phaeochromocytoma the mean night time blood pressure increased by 4/2 mm Hg. In patients with hypertension, primary hyperparathyroidism, and unoperated coarctation of the aorta the falls in blood pressure were normal. CONCLUSIONS--In normotensive subjects and those with primary hypertension there is usually a reduction in blood pressure at night. In all renal forms of secondary hypertension and in most endocrine forms the reduction in blood pressure is only a third to a half of normal. Patients with primary hyperparathyroidism and unoperated coarctation of the aorta show a normal reduction.     

The Angiotensin Infusion Test and Peripheral Venous Renin Activity

Forty hypertensive patients were studied to examine the assumption that the angiotensin pressor dose reflects endogenous renin activity. Peripheral renin activity was assayed by the method of Boucher et al.⁴ Sensitivity to the infusion of synthetic angiotensin II was determined as suggested by Kaplan and Silah.¹Sixteen patients with essential hypertension with normal renal angiography required 3.8 ng. angiotensin/kg./min. to raise the diastolic pressure 20 mm. Hg. All but one were sensitive to angiotensin infusion of less than 5 ng./kg./min. Renin activity was normal in all except in one sensitive subject. Angiotensin infusion response and mean renin activity in 13 patients with essential hypertension with abnormal renal angiography were similar to that of the first group. The pressor dose in 11 renovascular hypertensives was 9.8 ng./kg./min. All but three had elevated plasma renin activity.Our results suggest that: (1) the angiotensin infusion test is suitable for differentiating patients with true renovascular hypertension from those with essential hypertension with or without associated renal artery disease; (2) the angiotensin pressor dose correlates with the level of peripheral venous renin activity (p < 0.01).     

The effects of endotoxin on platelet-activating factor synthesis in cultured rat glomerular mesangial cells

Platelet-activating factor (PAF), a potent vasoactive phospholipid, may contribute to acute renal failure and septic shock accompanying endotoxemia. Rat glomerular mesangial cells in culture synthesize PAF and contract after the addition of PAF. We thus investigated the potential of mesangial cells to respond to Escherichia coli lipopolysaccharide endotoxin with enhanced PAF synthesis in vitro. The mesangial cells were incubated with [3H]acetate, substrate for lyso-PAF: acetyl-CoA acetyltransferase, and endotoxin at different concentrations for various periods of time at 37 degrees C. Lipids were extracted and PAF was isolated by thin-layer chromatography. Endotoxin stimulated PAF generation in a time- and dose-related manner. Whereas most of the PAF was associated with the cells, endotoxin more than doubled the amount of PAF released into the extracellular medium as compared to control. Furthermore, the PAF-like material obtained from endotoxin-stimulated mesangial cells irreversibly aggregated washed rabbit platelets. This effect was lost after alkaline methanolysis and was totally blocked by L-652,731, a specific PAF-receptor antagonist. Finally, the PAF-like material exerted a hypotensive effect, which was abolished by L-652,731, when infused intravenously into healthy rats. These data indicate that rat glomerular mesangial cells have the ability to synthesize PAF in response to endotoxin. This suggests that PAF, so generated within the glomerulus, may contribute to acute decrements of glomerular filtration rate in endotoxemia.     

Role of platelet-activating factor in the ovine heparin-protamine reaction.

Platelet-activating factor (PAF) infusion into sheep, as well as protamine reversal of heparin anticoagulation, causes thromboxane release into plasma, pulmonary hypertension, hypoxemia, and leukopenia. We investigated the possible role of PAF in the heparin-protamine reaction. Intravenous protamine was administered to neutralize heparin anticoagulation in five awake sheep and caused an increase of mean pulmonary arterial pressure from 16.6 +/- 1 (SE) mmHg at base-line to 47 +/- 9 mmHg at 1 min after protamine injection (P < 0.01) because of a 4.5-fold increase of pulmonary vascular resistance. This neutralization reaction induced a 25% reduction of circulating leukocyte count and arterial PO2. Undetectable blood levels of PAF were measured by bioassay and high-performance liquid chromatography during these heparin-protamine reactions. Infusion of BN 52021 (20 mg/kg), a PAF receptor antagonist, before rechallenging the same sheep with heparin and then protamine did not reduce the level of peak pulmonary hypertension or the degree of hypoxemia and leukopenia. We conclude that the leukopenia and thromboxane-mediated pulmonary vasoconstriction occurring after rapid intravascular formation of heparin-protamine complexes in sheep are not due to the release of PAF.     

Dietary fish oils reduce plasma levels of platelet activating factor precursor (lyso-PAF) in rats

The object of this study was to develop an assay for platelet activating factor (PAF) in rat plasma, and to utilise this to determine the effects of dietary fish oil on PAF in normotensive and spontaneously hypertensive rats. Measurement of platelet activating factor in blood plasma has proved difficult because of its rapid hydrolysis in vivo to lyso PAF. We describe here a method based on the prior acetylation of lyso PAF extracted from plasma to PAF before bioassay using 14C-serotonin labelled platelets. The active material found in acetylated plasma extracts was characterized as PAF by its chromatographic mobility, the action of phospholipases A2, C and D and by cross-desensitization studies with rabbit platelets. Rats fed dietary fish oil ('max EPA') had significantly decreased plasma lyso-PAF levels compared to control animals fed hydrogenated coconut oil (HCO). Serum thromboxane B2 (TXB2) levels were also significantly lower in animals fed the 'max EPA' diet. Spontaneously hypertensive rats (SHR) had significantly lower plasma lyso-PAF levels than their normotensive Wistar Kyoto (WKY) controls maintained on the same diets. It is proposed that dietary alterations in PAF synthesis may influence platelet behaviour in addition to the well described effects of dietary fish oil on the proaggregatory prostanoid TXA2. Rat strain differences in lyso-PAF synthesis occur, but are unlikely to be related to the maintenance of hypertension in SHR.