Excess prevalence of extracranial carotid artery lesions in renovascular hypertension.

High renin hypertension has been associated with a higher risk of stroke than low-to-normal renin hypertension. Accordingly, we investigated prospectively the prevalence of the extracranial carotid artery lesions in a case-control study of 70 patients (38 women and 32 men, aged 16 to 77 years) without history or symptoms of cerebrovascular disease. Renovascular hypertension was diagnosed in 35 patients on the basis of the angiographic demonstration of renal artery stenosis and of the favorable outcome after revascularization. It was caused by atherosclerosis in 20 patients and by fibrodysplasia in 15. Each renovascular hypertensive patient was individually matched with a control with primary hypertension for sex, race, age, blood pressure levels, duration of hypertension, smoking, diabetes mellitus, total serum cholesterol, and triglycerides. Carotid arteries were evaluated by a High Resolution Duplex system (Biosound 2000, probe 4 cm, 8 mHz). Our results show that after the matching the two groups were similar in terms of demographic features and overall cardiovascular risk profile (all P = NS). In renovascular hypertensives the prevalence of carotid artery lesions (82.6%) was significantly (P less than .01) higher than in primary hypertensives (42.9%). The higher prevalence of lesions in renovascular hypertension was observed not only in patients with atherosclerosis (100% v 55%, P less than .001), but also in those with fibrodysplasia (57% v 27%, P less than .01). Thus, for the same demographic features and overall cardiovascular risk profile, renovascular hypertension carries a more detrimental effect on the carotid artery than primary hypertension.     

Diagnostic value of plasma renin activity and plasma angiotensin II in renovascular hypertension.

The plasma renin activity in both peripheral venous blood and the renal vein of the involved kidney showed high values. Angiotensin infusion elevated the urine volume and angiotensin excretion on the intact side, and the difference in urine volume and angiotensin excretion between the two sides was accentuated after angiotensin infusion. These findings are useful for the diagnosis of the stenotic side in renovascular hypertension. No difference in the prognosis of extirpation of the involved kidney and of vascular reconstruction of the stenotic artery was found for the treatment of renovascular hypertension. However, autotransplantation of the involved kidney was found to be more useful, since it allowed improvement of renal circulation, suppression of thrombosis formation, and the maintenance of kidney tissue.     

Prostaglandin E2, renin and angiotensin II in renovascular hypertension

We studied a group of 12 hypertensive patients (seven men, five women) with unilateral renal arterial stenosis, and evaluated the morphological criteria on renal angiography for the significance of the stenosis and compared them with the prostaglandin-E2 (PGE2), plasma renin activity (PRA), and angiotensin II (ANG II) concentrations in both renal veins. PGE2 and PRA concentrations were significantly higher in renal veins of kidneys with arterial stenosis with patients supine and after sitting up for 15 min, but the ANG II concentration was raised only with the patient sitting. Assuming that a PRA ratio greater than 2 signifies stenosis of haemodynamic importance, correlation to the angiographic classification was seen in 11 of the 12 patients. The PGE2 ratios were better correlated to PRA ratios than to the angiographic findings. ANG II ratios showed an inconstant and variable pattern in relation to the morphological picture. Our results confirm that PGE2 concentrations in renal venous blood increase in parallel to PRA, and may be interpreted as a means of preserving the blood flow in a kidney with arterial stenosis. However, it is unclear whether this increase is the result of dilution factors or of increased net production of PGE2. Determination of PGE2 in renal vein blood apparently gives no additional information about the functional significance of renal arterial stenosis, and PRA determinations remain the best guide in the management of renovascular hypertension.     

Effect of angiotensin on renal transport of sodium in renovascular hypertension

Eleven patients with renovascular arterial hypertension were studied, 9 of whom had unilateral renal artery stenosis and 2 bilateral renal artery stenosis.

Angiotensin increased sodium excretion in the contralateral kidney and did not change it in the stenotic one.

In bilateral stenosis angiotensin increased sodium excretion significantly in both kidneys.

The difference in response to angiotensin between patients with unilateral stenotic kidney and those with bilateral stenosis is apparently unrelated to arterial blood pressure distal to the arterial stenosis.     

Renal sympathetic neuroeffector function in renovascular and angiotensin II-dependent hypertension in rabbits

We tested the hypotheses that the gains of specific renal sympathetic neuroeffector mechanisms are altered in secondary hypertension and that the nature of these alterations depends on the precise experimental setting of the kidney. Rabbits were sham operated, or made comparably hypertensive (mean arterial pressure increased 17% to 24%) by clipping the left or right renal artery or by chronic infusion of angiotensin II (20 to 50 ng kg(-1) min(-1) SC). Four to 6 weeks later, under pentobarbital anesthesia, the left renal nerves were sectioned and electrically stimulated at low (0 to 2 Hz) and high (4 to 8 Hz) frequencies. Neurally evoked reductions in total renal blood flow, cortical perfusion, urine flow, and sodium excretion and increases in renal norepinephrine spillover were not significantly greater in kidneys of hypertensive rabbits than normotensive controls. Neurally evoked increases in renal renin release and the slope of the relationship between renin release and norepinephrine spillover were less in kidneys of hypertensive rabbits than normotensive controls. Low-frequency renal nerve stimulation reduced medullary perfusion, which was negatively correlated with renal norepinephrine spillover in kidneys from all 3 groups of hypertensive rabbits but not normotensive controls. Two-hertz stimulation reduced medullary perfusion by 19% in hypertensive rabbits but not in normotensive rabbits. Thus, of all of the renal sympathetic neuroeffector mechanisms studied, only neural control of medullary perfusion was enhanced in these models of secondary hypertension. This effect appears to be mediated postjunctionally, not through enhanced neural norepinephrine release, and may contribute to the development and/or maintenance of hypertension in these models.     

Differential renal function during angiotensin converting enzyme inhibition in renovascular hypertension

Renal function was measured sequentially in 32 patients with proven renovascular hypertension who were treated with the oral angiotensin converting enzyme inhibitor captopril. Renal function was assessed by serial measurement of serum creatinine. Six patients showed acute rises in serum creatinine concentration compatible with acute renal failure. Acute renal failure was confined to those patients with stenosis to a solitary kidney (transplant or native, occurring in 3 of 8 patients) or bilateral renal artery stenosis (occurring in 3 of 13 patients). No rise in serum creatinine concentration was observed in 11 patients with unilateral renal artery stenosis during long-term angiotensin converting enzyme inhibitor therapy. Acute renal failure during angiotensin converting enzyme inhibitor therapy was not related to the degree of blood pressure fall or the plasma angiotensin II level. Eleven patients with renovascular hypertension were followed prospectively with estimation of renal function by 99mTc-diethylenetriaminepentaacetic acid (DTPA) clearance (determined by computer analysis of scintillation camera renography). In six patients with unilateral renal artery stenosis, total 99mTc-DTPA clearance and serum creatinine level remained constant following angiotensin converting enzyme inhibitor therapy, while in five patients with bilateral renal artery stenosis 99mTc-DTPA clearance fell from 40 +/- 9 to 27 +/- 5 ml/min (p less than 0.05). Split renal function studies revealed that 99mTc-DTPA clearance fell in most kidneys with stenosed arteries during angiotensin converting enzyme inhibition, including the stenosed kidney from patients with unilateral renal artery stenosis (16 stenosed kidneys studied; change in Tc-DTPA clearance, -7.5 +/- 2.7 ml/min).(ABSTRACT TRUNCATED AT 250 WORDS)     

Left ventricular structural characteristics in unilateral renovascular hypertension and primary aldosteronism

To assess the importance of the renin-angiotensin system and plasma volume as determinants of hypertensive left ventricular hypertrophy and its anatomy, patients with unilateral renovascular hypertension and primary aldosteronism were studied by echocardiography. Blood pressure, age and sex were matched as closely as possible. The 19 patients with unilateral renovascular hypertension and the 19 patients with primary aldosteronism were similar in age, sex and blood pressure (168 +/- 19/97 +/- 11 and 163 +/- 17/99 +/- 10 mm Hg, respectively), but plasma volume was increased in the patients with primary aldosteronism. Interventricular septal thickness, left ventricular posterior wall thickness, left ventricular mass index and relative wall thickness did not differ between the 2 groups of patients. There was a significant correlation between the level of systolic blood pressure and either left ventricular mass index (r = 0.34, p less than 0.05) or relative wall thickness (r = 0.58, p less than 0.001) in both groups of patients. Left ventricular end-diastolic dimension index was increased in the patients with primary aldosteronism compared with those with unilateral renovascular hypertension (3.2 +/- 0.4 vs 2.9 +/- 0.3 cm/m2, p less than 0.02). When confined to the patients with systolic pressure greater than or equal to 150 mm Hg, relative wall thickness was significantly increased in the patients with unilateral renovascular hypertension. Patients with primary aldosteronism and unilateral renovascular hypertension of similar blood pressure levels, age and sex have almost identical degrees of left ventricular hypertrophy and anatomy. In contrast, the patients with primary oldosteronism had increased left ventricular dimension index.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reactive hyperreninemia in renovascular hypertension after angiotensin blockage with saralasin or converting enzyme inhibitor.

Baseline plasma renin activity and responses to saralasin and converting enzyme inhibitor SQ 20881 (teprotide) in 47 untreated patients with surgically correctable renovascular hypertension were compared to those in 100 patients with high- and normal-renin essential hypertension. All 32 renovascular patients on normal sodium intake had high renin-sodium profiles and renin values greater than or equal to 5 ng angiotensin I/mL.h, as compared to 20 of 64 with essential hypertension. Diagnostic discrimination was greatly enhanced by infusion of saralasin or SQ 20881, which elicited marked reactive hyperreninemia in 31 of 32 renovascular patients but in only two of 64 with essential hypertension. Reactive hyperreninemia appeared to be more a specific test for renovascular hypertension than depressor responses. Prior dietary sodium depletion abolished this specificity. The results suggest that after initial screening with renin measurements, testing with angiotensin blocking agents may be a useful secondary screening procedure for more invasive and definitive procedures.     

Current concepts in renovascular hypertension.

Renovascular disease represents an important dimension of hypertension. Although estimates vary regarding the exact prevalence of renovascular hypertension, it is being diagnosed with increasing frequency because of refined criteria for the workup and the availability of sensitive diagnostic tests. Two major pathologic entities--atherosclerosis and fibromuscular dysplasia--account for most cases of renovascular hypertension. Once the diagnosis and clinical significance of renal artery stenosis in a hypertensive patient are established, appropriate and specific therapy should be considered. The goal is not only to treat hypertension, but to preserve and restore renal function. Although antihypertensive drug therapy may lower the blood pressure, reperfusion of the kidney (surgical, angioplasty) is a desirable long-term objective in the management of patients with renovascular hypertension. With careful selection of therapeutic choices, we are now able to render optimal care to patients with renovascular hypertension.     

Abdominal bruits in renovascular hypertension.

A study of 87 patients surgically treated for renal arterial stenosis revealed that upper abdominal bruits were heard more frequently in patients whose stenosis was due to fibrous disease than to atherosclerosis. A diastolic bruit in a patient with fibrous disease of the renal artery usually indicated a favorable surgical result. Conclusions regarding the prognostic value of diastolic bruits in atherosclerotic renal artery disease must be deferred until a larger number of patients with this finding can be studied. When hypertension of less than 3 year's duration was combined with presence of a diastolic bruit, 17 or 18 patients had a favorable surgical outcome. An abdominal bruit should be carefully sought for in all patients evaluated for hypertension; when found, should be characterized acurately, because of the important diagnostic and prognostic information it may provide.     

Sitagliptin augments sympathetic enhancement of the renovascular effects of angiotensin II in genetic hypertension

Dipeptidyl peptidase IV converts neuropeptide Y(1-36) (Y(1)-receptor agonist released from renal sympathetic nerves) to neuropeptide Y(3-36) (selective Y(2)-receptor agonist). Previous studies suggest that Y(1), but not Y(2), receptors enhance renovascular responses to angiotensin II in kidneys from genetically-susceptible animals. Therefore, we hypothesized that inhibition of dipeptidyl peptidase IV with sitagliptin (antidiabetic drug) would augment the ability of exogenous and endogenous neuropeptide Y(1-36) to enhance renal vascular responses to angiotensin II in kidneys from spontaneously hypertensive rats. This hypothesis was tested using 3 protocols in isolated perfused kidneys. Results from Protocol 1: Exogenous neuropeptide Y(1-36) enhanced renovascular responses to angiotensin II. This effect of neuropeptide Y(1-36) was blocked by BIBP3226 (selective Y(1) receptor antagonist); Exogenous neuropeptide Y(3-36) did not enhance renovascular responses to angiotensin II. Results from Protocol 2: Sitagliptin augmented the ability of exogenous neuropeptide Y(1-36) to enhance renovascular responses to angiotensin II. This effect of sitagliptin was blocked by BIBP3226. Results from Protocol 3: Renal sympathetic nerve stimulation enhanced renovascular responses to angiotensin II; this enhancement was augmented by sitagliptin and abolished by BIBP3226. Neuropeptide Y(1-36) via Y(1) receptors enhances renovascular responses to angiotensin II in kidneys from genetically hypertensive animals. Sitagliptin, by blocking dipeptidyl peptidase IV, prevents metabolism of neuropeptide Y(1-36) and thereby increases the effects of neuropeptide Y(1-36) released from renal sympathetic nerves on Y(1) receptors leading to augmentation of neuropeptide Y(1-36)-induced enhancement of the renovascular effects of angiotensin II. The renal effects of dipeptidyl peptidase IV inhibitors in hypertensive diabetic patients merit a closer examination.     

Conversion of inactive renin to active renin following acute angiotensin converting enzyme inhibition in essential hypertension and renovascular hypertension

The physiological role of inactive renin, especially the question of whether and how a conversion to active renin takes place in vivo, remains controversial. In order to show the dynamic alterations from inactive to active renin following acute ACE-inhibition, both forms of renin were investigated in both renal veins and the peripheral circulation of 20 patients with essential hypertension and 20 patients with renovascular hypertension before and 1 h after 25 mg of captopril. Active and inactive renin were determined indirectly as plasma renin activity (PRA, unit: ng/ml x h). In vitro activation of inactive renin was achieved with trypsin (1 mg/ml plasma), followed by a further determination of PRA (= total renin). Subtraction of the active renin from the total renin yields the amount of inactive renin. In patients with essential hypertension, the mean values of active renin increase equally in both renal veins (1.4 and 1.3 before, 1.9 and 1.8 after captopril) and the peripheral circulation (0.9 and 1.3) (p less than 0.002), whereas the inactive renin decreases correspondingly. Renal veins: 7.6 and 8.2 before, 7.2 and 7.6 after captopril; peripheral circulation: 7.7 before and 7.0 after captopril (p less than 0.05). In all patients with renovascular hypertension, there is basally a marked lateralization of active renin (6.4 vs 3.5; p less than 0.01) and inactive renin (20.5 and 18.9, p less than 0.03) towards the side of the ischemic kidney. After captopril, the values for total renin and active renin increase (p less than 0.001), and the side difference for active renin becomes still more pronounced (33.0 vs 14.2; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)