Renal actions of angiotensin II in renovascular hypertension

In renal artery stenosis severe enough to cause hypertension, angiotensin II maintains glomerular filtration rate (GFR) both in the initial high renin phase of hypertension and later when plasma levels are normal. Angiotensin II also maintains GFR in less severe stenosis, which does not cause hypertension. This homeostatic action of angiotensin II to maintain GFr has minimal effects on blood flow. In renal-wrap hypertension, plasma renin levels are elevated for longer than after renal artery stenosis, but in other respects this initial phase of the hypertension is similar to that after renal artery stenosis. GFR is reduced, the rate of development of hypertension is accelerated by angiotensin II, and angiotensin II maintains the glomerular filtration fraction. Renal resistance is markedly increased owing to both compression of the kidney by the hypertrophying renal capsule and to angiotensin II. Thus angiotensin II apparently plays a primarily homeostatic role in renovascular hypertension to maintain glomerular ultrafiltration. It is suggested that the angiotensin II may be formed intrarenally and may act on sites other than resistance blood vessels.     

Reversal of renovascular hypertension: role of the renal medulla

The fall in blood pressure, which occurs when renovascular hypertension is corrected surgically, offers a means of elucidating the factors responsible for blood pressure control. When Goldblatt two-kidney, one-clip hypertension in the rat is reversed by unclipping the renal artery, or by removal of the ischaemic kidney, restoration of normal blood pressure is due to a fall in peripheral resistance. This is associated with sodium retention and cannot be modified by inhibition of the renin-angiotensin system. The fall is, however, partially inhibited by chemical removal of the renal medulla by means of 2-bromo-ethylamine hydrobromide. When normal rats are chemically medullectomized, moderate hypertension is produced, which cannot be attributed to the renin-angiotensin system or sodium retention. It is concluded that a renomedullary vasodepressor system is ablated by chemical medullectomy: further, this system plays a role in the surgical correction of Goldblatt hypertension.     

Blockade of renin or angiotensin for understanding human hypertension: a comparison of propranolol, saralasin and converting enzyme blockade.

To understand the role of the renin-angiotensin-aldosterone system in the pathogenesis of human hypertension, in serial studies we have blocked the system using three different pharmacologic probes: 1) reduction of renin secretion by administration of the beta receptor blocker, propranolol; 2) blockade of the action of angiotensin II by infusion of saralasin, a competitive antagonist of angiotensin II; and 3) blockade of the enzymatic conversion of angiotensin I to angiotensin II by infusing a nonapeptide competitive inhibitor. The depressor responses induced by either propranolol or the nonapeptide expose a significant to major involvement of excess renin--angiotensin in maintaining the hypertension of some 50 to 70% of common forms of hypertension including "essential" hypertension. This subgroup includes nearly all patients with high or "normal" renin--sodium profiles. The considerably lower estimates for a renin factor in essential hypertension suggested by saralasin testing now appear due to the partial agonism of this drug. Further studies are required to determine whether this relative or absolute excess of renin secretion is primarily involved in the hypertension and if not why it fails to shut itself off. Similar studies of normal subjects are also needed to determine whether renin support of blood pressure is proportionately greater or less than in hypertensive subjects. Meanwhile the validation provided by these three different pharmacologic probes portends a burgeoning clinical role for renin--sodium profiling not only in screening for renal and adrenal cortical hypertensions but also for characterizing the vasoconstrictor and volume elements involved in various individual patients and thus enabling more specific treatments of the various subtypes of essential hypertension.     

Humoral and neurogenic factors in two-kidney renovascular hypertension

A "bolus" dose (110 microgram) of the angiotesin II (A II)-blocker 1-Sar-8-Ala-A II (Saralasin, S) followed by its slow rate infusion (5 microgram/min/rat) for thirty min, was injected before and after the complete ganglionic blockade by pentolinium (P) in unanaesthetized unilaterally clipped renal hypertensive rats (the opposite kidney remained untouched). Pentolinium was also injected like a "bolus" dose (3 mg) followed by slow infusion (0.1 mg/min/rat) for thirty min. The observations were made until the fifth week after clipping the left renal artery. A consistent maximal hypotensive response was observed after the "bolus test" with both drugs. When S was the first drug injected, an inverse correlation was found between the percent decrease in arterial pressure (BP) by S and the percent decrease in BP by P (r = --0.83, P < 0.01, n = 8). Thus whenever a greater hypotensive effect was obtained by S, a smaller neural pressor component remained to be blocked by P. On the other hand, when P was the first drug injected a lesser A II pressor component remained to be blocked by S in the hypertensive rats. The results suggest that a considerable A II pressor effect in two-kidney renovascular hypertension is mediated via neurogenic mechanisms from the first week. A direct pressor vasoconstriction was found to be significant in cases with very high plasma-renin activity.     

Captopril in renovascular hypertension: long-term use in predicting surgical outcome.

The angiotensin converting-enzyme inhibitor captopril was used as long-term preoperative treatment in a series of hypertensive patients with unilateral renal arterial disease. There were immediate and sustained falls in plasma angiotensin II and aldosterone concentrations, with converse increases in circulating renin and angiotensin I. In patients with sodium and potassium deficiency and secondary aldosterone excess before treatment captopril corrected the sodium and potassium deficits; in these cases the initial hypotensive response was profound but the later effect was less pronounced. When sodium and potassium state was initially normal it remained unchanged during captopril treatment, while the full hypotensive effect took up to three weeks to be attained. The immediate, but not long-term, falls in arterial pressure with captopril were proportional to the immediate decrements of plasma angiotensin II. Nevertheless, while the immediate blood-pressure reduction with captopril variously overestimated and underestimated the eventual surgical response, the absolute blood-pressure values during long-term captopril related well with those after operation. Pretreatment plasma renin and angiotensin II concentrations, while closely predicting the immediate captopril response, are fallible guides to surgical prognosis. In contrast, long-term treatment with converting-enzyme inhibitors may provide an accurate indication of surgical outcome.     

Participation of the renin-angiotensin system in experimental renovascular hypertension

Hypertension was induced in Wistar rat by means of a clip in the left renal artery. After two weeks (acute stage) and sixteen weeks (chronic stage) the animals had a significant increase in arterial pressure (AP) and plasma renin activity (PRA). At both stages, nephrectomy or revascularization of the ischemic kidney returned AP and PRA to the normal level, both in the short term (1 day) and long term (60 days).     

Effects of renovascular hypertension on reproductive function in male rats

OBJECTIVE: The present study investigated the effects of renovascular hypertension (2K/1C model) on the reproductive function of male rats, represented by sexual behavior, plasma prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone, and spermatogenesis. METHODS: The present experiments were performed to investigate the reproductive function of 2K/1C male Wistar rats and compare with 2K/1C male rats successfully treated for hypertension with nifedipine and was divided in the following groups: (1) Sham+V (n=10): Sham-operated males with vehicle used; (2) Sham+N (n=13): Sham-operated males treated with nifedipine (10 mg/kg/day); (3) 2K/1C+V (n=14): 2K/1C-operated males with vehicle used; and (4) 2K/1C+N (n=16): 2K/1C-operated males treated with nifedipine. RESULTS: The data indicated an association between hypertension induced by the 2K/1C model and reduction of reproductive function, as demonstrated by an impairment of sexual behavior, higher plasma PRL and lower plasma testosterone and FSH. The treatment with nifedipine prevented the reduction of sexual behavior and the increase of plasma PRL, but did not alter the reduction of plasma testosterone and FSH and spermatogenesis of 2K/1C rats. CONCLUSIONS: Reproductive function is adversely affected in the 2K/1C animal model, and high blood pressure plays a role in the modulation of plasma PRL and sexual behavior. Moreover, other events, without high blood pressure, but with high plasma renin activity associated with the 2K/1C model, contribute directly to the reduction of plasma testosterone and FSH and impaired spermatogenesis.     

Magnetic resonance tomography in the diagnosis of renovascular hypertension]

MR tomography was used for investigation of 38 patients with renovascular hypertension (RVH) and 26 healthy persons. A possibility of the use and practical value of the method in the diagnosis and evaluation of renal function and renal arteries (RA) were under study. Some quantitative MRT indices were calculated both for the patients and healthy persons. They included spin-spin relaxation time, proton density, and signal intensity. These data can provide important information on renal function in RVH with relation to kidney sizes and the state of the renal parenchyma (evaluation of the cortical substance and medulla and the border between them). In some cases MRT ensures noninvasive diagnosis of PA stenosis.     

Renal extraction of circulating adiponectin in patients with renovascular hypertension

BACKGROUND: Patients with chronic renal failure are characterized by an elevated plasma adiponectin concentration, which is significantly lowered after successful kidney transplantation. The direct renal clearance and extraction of adiponectin have not yet been documented in humans. Therefore the aim of the study was to estimate separate kidney extraction of adiponectin, by measuring its concentration in the aorta and both renal veins, in patients with renovascular hypertension caused by unilateral renal artery stenosis. METHODS: In 30 patients with significant (> 70%) unilateral renal artery stenosis, plasma adiponectin was measured in blood samples taken from the aorta, both renal veins and the vena cava inferior below the orifices of the renal veins. RESULTS: Renal venous plasma adiponectin concentrations (both from the kidney with renal artery stenosis and from the contralateral organ) were only numerically lower than the concentrations measured in the aorta (11.10 [8.65-13.56]; 11.12 [8.81-13.42]; 11.35 [8.90-13.80] microg/ml, respectively). Fractional extraction of adiponectin was 5.0 [-1.6-11.0]% in the kidney with renal artery stenosis and 3.0 [-2.4-9.01% in the contralateral "normal" kidney. Slightly higher concentrations of plasma adiponectin were observed in the vena cava inferior below the orifices of the renal veins (11.79 [9.14-14.44] microg/ml). In patients with unilateral renal artery stenosis significant negative correlations were found between plasma adiponectin concentration obtained from the vena cava inferior below the orifices of renal veins and eGFR (r = -0.38; p < 0.05), systolic (r = -0.71; p < 0.0001) and diastolic blood pressure (r = -0.40; p < 0.04), as well as serum triglyceride concentrations (r = -0.64; p < 0.001). CONCLUSION: The findings indicate that the fractional renal extraction of adiponectin is rather low.