The effect of splanchnic block on renin production and renal haemodynamics in hypertensive patients

In eighteen patients with hypertension the effect of a splanchnic block was studied with respect to the plasma renin activity (PRA) in the renal vein and to the renal haemodynamics. A significant reduction of the PRA was noted during splanchnic block, both in kidneys with arterial stenosis, and in those without. The decrease in renin activity took place despite a simultaneous decrease in renal vascular resistance, which in itself should increase the secretion of renin. This supports the view that the sympathetic nervous system dominates over the baroreceptors in patients with hypertension at the pressure levels investigated and if the sodium intake is restricted.     

Acute kidney injury: new concepts. Hepatorenal syndrome: the role of vasopressors

Type 1 hepatorenal syndrome (HRS) is prerenal failure specific to decompensated cirrhosis. In patients with HRS, there is marked splanchnic/systemic vasodilation resulting in arterial hypotension, arterial baroreceptor unloading, overstimulation of the sympathetic nervous and renin-angiotensin systems. This reflex neurohumoral hyperactivity via endogenous vasoconstrictors/vasopressors such as angiotensin II and noradrenaline induces arterial vasoconstriction in different extrasplanchnic vascular beds (including preglomerular arteries in the kidneys). Decreased arterial pressure (i.e. low renal perfusion pressure) and preglomerular vasoconstriction are thought to play a major role in the decline of the glomerular filtration rate (GFR). Nonrandomized studies in patients with HRS have shown that the administration of a splanchnic vasoconstrictor (vasopressin analogue or alpha(1)-adrenoceptor agonist), usually combined with intravenous albumin, causes increases in arterial pressure, arterial baroreceptor uploading, decreased neurohumoral activity, decreased renal vascular resistance, and increased GFR. Randomized clinical trials have shown that treatment with a combination of the vasopressin analogue terlipressin and intravenous albumin improves renal function in patients with type 1 HRS. Vasopressor therapy with terlipressin plus intravenous albumin is the medical treatment of choice for type 1 HRS.     

Autonomic nervous dysfunction in essential hypertension

Borderline hypertension, a condition in which the blood pressure oscillates between normal and high values, is a predictor of future more severe hypertension. Pathophysiologically, borderline hypertension is different from established hypertension. A large proportion of such patients have elevated cardiac output and a normal vascular resistance. In established hypertension, the output is normal and resistance is elevated. The elevation of cardiac output in borderline hypertension is neurogenic; it can be abolished by an autonomic blockade of the heart. In addition to an increased cardiac sympathetic drive, increased sympathetic tone to the kidney, arterioles, and veins has also been found. In parallel with the hypersympathetic state, patients with borderline hypertension also show decreased parasympathetic tone. The enhanced sympathetic tone leads to a decreased cardiac responsiveness, and eventually, the cardiac output returns to the normal range. High blood pressure causes vascular hypertrophy, and hypertrophic vessels are hyperresponsive to vasoconstriction. These secondary changes in the responsiveness of the heart and blood vessels are the basis of transition from a high cardiac output to high-resistance hypertension. These hemodynamic changes are associated with a downregulation of the sympathetic tone. A picture of an apparently nonneurogenic high-resistance hypertension emerges. Nevertheless, when assessed in regard to the enhanced pressor responsiveness, the sympathetic drive in such patients is still excessive. Despite the apparently normal tone, the sympathetic nervous system continues to play an important pathophysiological role in established hypertension. Borderline hypertension is associated with numerous metabolic abnormalities including obesity and insulin resistance. It is tempting to view all these abnormalities as a common expression of the increased sympathetic drive in hypertension. Explanation of the basis of the association of hypertension and metabolic abnormalities promises to bring new insights into the pathophysiology of two common diseases of civilization: hypertension and diabetes mellitus.     

Obesity hypertension

Obesity and hypertension are two major risk factors for the cardiovascular system. Whereas arterial hypertension increases afterload to the left ventricle, obesity produces an increase in stroke volume and increases preload. As a result of this double burden, the heart adapts with eccentric left ventricular hypertrophy. Contractility becomes impaired early in the course of obesity hypertension, and ventricular ectopy is observed. As a consequence, the obese hypertensive patient is at a high risk for congestive heart failure and sudden death. Despite the synergistic effects of obesity and hypertension on the heart, patients appear to be relatively protected from nephrosclerosis and coronary artery disease. These epidemiologic observations are supported by the pathophysiologic changes that take place in obesity hypertension. At any given level of arterial pressure, cardiac output and renal blood flow are elevated in obese hypertensive patients, whereas systemic and renal vascular resistance are decreased when compared to lean hypertensive patients. Because total peripheral resistance is considered the hemodynamic hallmark of arterial hypertension, systemic vascular complications may be less pronounced in obesity hypertension. Weight loss decreases preload, afterload to the left ventricle, and the sympathetic drive to the heart. Protecting the heart from these hypertrophic stimuli should be a major goal of preventive cardiology.     

Progressive renovascular hypertension by increasing aortic constriction in rats

Moderate and progressive hypertension was produced experimentally in rats by progressive aortic constriction. The progression of the stenosis was assessed by the differences of pressure across the stenosis. Haemodynamic studies were performed 15, 30 and 60 days after the ligature was placed or after sham operation. Fifteen days after surgery, when the ligated rats did not show any increase in carotic pressure, they showed augmented cardiac output (50.3 +/- 5.4 v. 29.7 +/- 2.0 ml min-1 100 g-1; mean +/- -SEM) and a decreased total peripheral resistance (2.23 +/- 0.21 v. 3.67 +/- 0.20 mmHg ml-1 min 100 g). They also had decreased vascular resistance in both kidneys and in skeletal muscle samples above and below the ligature as well as increased plasma renin content and normal values of plasma volume and extracellular volume. Later in the evolution of hypertension, carotic pressure and the pressure gradient across the stenosis increased (51.8 +/- 4.5 v. 0.9 +/- 1.6 mmHg in controls), cardiac output decreased to control values, total peripheral resistance as well as renal and muscular vascular resistances increased. Plasma and extracellular volume remained unchanged in ligated rats in contrast to controls where they decreased. Perfusion pressure of the kidney below the ligature did never fall below control values (97.2 +/- 3.4 v. 100.4 +/- 2.4 mmHg). A small but constant degree of elastosis and a double layer of myocytes in the renal arterioles above the ligature was the only histological finding.     

Renal artery stenosis due to fibromuscular dysplasia in a transplanted kidney from a deceased donor: A difficult diagnosis at color doppler ultrasonography

Atherosclerotic renal artery stenosis is a frequent cause of arterial hypertension and/or allograft dysfunction after kidney transplantation and is usually located at the iliac artery anastomosis. Fibromuscular dysplasia is a less frequent, nonatherosclerotic, vascular disease, inducing stenosis at the proximal/mid‐distal part of the renal artery. We report the case of a 44‐year‐old woman, in whom serum creatinine concentration increased and arterial hypertension developed 3 months after renal transplantation. Color Doppler ultrasonography showed a low arterial resistance index and prolonged acceleration time in the interlobar arteries, and a significantly increased peak systolic velocity at the mid third of the renal artery, demonstrating hemodynamically significant stenosis. Percutaneous transluminal angioplasty allowed stenosis correction and was followed by creatinine concentration and arterial blood pressure normalization. © 2013 Wiley Periodicals, Inc. J Clin Ultrasound 42 :116–120, 2014     

Split intrarenal hemodynamics in renovascular hypertension.

Split intrarenal hemodynamics in stenotic and contralateral kidneys of unilateral renovascular hypertension (RVH) were estimated by Gomez's formulae. Ten patients with RVH were studied. Split para-amino hippurate and inulin clearances were measured by ureteral catheterization as indexes for renal plasma flow and glomerular filtration rates, allowing the estimation of intrarenal hemodynamics such as preglomerular arteriolar resistance, postglomerular arteriolar resistance and glomerular hydrostatic pressure in each kidney. Renal plasma flow and glomerular filtration rates were lower in the stenotic kidney (83 +/- 12, 19 +/- 2 ml/min/m2) than in the contralateral kidney (170 +/- 19, 43 +/- 4). Preglomerular arteriolar resistance was elevated due to the stenotic lesion in the stenotic kidney (30,900 +/- 4,500 dyns.sec.cm-5) while the elevation in the contralateral kidney (11,300 +/- 1,000) was less. Postglomerular arteriolar resistance was high in both kidneys. Glomerular pressure was lowered in the stenotic kidney (54 +/- 1 mmHg), while elevated in the contralateral kidney (71 +/- 3). Although the stenotic kidney of RVH was protected from systemic hypertension (138 +/- 6 mmHg) by stenosis of the renal artery, the increase in preglomerular arteriolar resistance in the contralateral kidney was not sufficient, making glomerular pressure elevated. Thus, glomerular hypertension and hyperfiltration were demonstrated in the contralateral kidney of RVH.     

Essential hypertension: neural considerations

Current evidence suggests that the sympathetic nervous system plays a predominant role in some fraction of essential hypertension. Patients in whom such mechanisms are likely to be operative are young people with mild or labile hypertension. These mechanisms are expressed clinically through orthostatic hypertension, rapid heart rate, modestly elevated cardiac output, and normal or slightly elevated peripheral vascular resistance. The vascular resistance is inappropriately high for the level of cardiac output, and this is reflected in a mildly elevated blood pressure. This evidence carries therapeutic implications and suggests that sympatholytic drugs should be the first line of therapy. An additional pressor mechanism may arise from increased sympathetic activity along renal efferent nerves that impairs sodium excretion and another possible mechanism is stimulation of brain centers through impulses from the kidneys carried in renal afferent nerves.     

Enhanced sympathetic nervous activity after intravenous propranolol in ischaemic heart disease: plasma noradrenaline splanchnic blood flow and mixed venous oxygen saturation at rest and during exercise

To study the mechanisms by which acute beta-adrenergic blockade may change the activity of the sympathetic nervous system we have measured haemodynamic responses including splanchnic blood flow in twenty-three patients with ischaemic heart disease at rest and during supine exercise before and after i.v. injection of 0.039 mmol (10 mg) dl-propranolol. After propranolol both at rest and on exercise blood pressure, cardiac output and heart rate decreased, while splanchnic vascular resistance increased; mixed venous oxygen saturation decreased whilst arterial oxygen saturation and oxygen uptake were unchanged. Plasma noradrenaline increased after propranolol, values correlating with mixed venous oxygen saturation and splanchnic vascular resistance, both at rest and during exercise before and after propranolol, only at rest was there any correlation with arterial blood pressure. The increase in sympathetic nervous activity after propranolol may be due to a reduction in cardiac output and thereby alteration of the metabolic state (oxygen or related factors) in tissues. Afferent neural signals from the tissues may play a significant role in the regulation of sympathetic nervous activity.     

Edema in liver disease

Patients with advanced cirrhosis show an abnormal regulation of extracellular fluid volume, resulting in the accumulation of fluid as ascites or edema. As portal hypertension develops, splanchnic arterial vasodilation also does due mainly to the production of nitric oxide (NO). Splanchnic arterial vasodilation decreases effective arterial blood volume, leading to fluid accumulation and renal function abnormalities which are a consequence of the homeostatic activation of vasoconstrictor and antinatriuretic factors. And the net effect is retention of sodium and water as well as renal vasoconstriction. The portal hypertension and splanchnic hyperdynamic circulation elevate the pressure of the splanchnic capillary circulation, leading to the accumulation of retained fluid as ascites.     

ETA receptors mediate vasoconstriction,whereas ETB receptors clear endothelin-1 in the splanchnic and renal circulation of healthy men

The contribution of the endothelin (ET) receptors ET(A) and ET(B) to basal vascular tone and ET-1-induced vasoconstriction in the renal and splanchnic vasculature was investigated in six healthy humans. ET-1 was infused alone and in combination with the selective ET(A) receptor antagonist BQ123 or the selective ET(B) receptor antagonist BQ788 on three different occasions. BQ123 did not affect basal arterial blood pressure, splanchnic vascular resistance (SplVR) or renal vascular resistance (RVR), but inhibited the increase in vascular resistance induced by ET-1 [64+/-18 versus -1+/-7% in SplVR ( P <0.05); 36+/-6 versus 12+/-3% in RVR ( P <0.0001)]. BQ788 increased basal SplVR and RVR [38+/-16% ( P =0.01) and 21+/-5% ( P <0.0001) respectively], and potentiated the ET-1-induced vasoconstriction. Plasma ET-1 increased more after ET(B) blockade than under control conditions or after ET(A) blockade. These findings suggest that the ET(A) receptor mediates the splanchnic and renal vasoconstriction induced by ET-1 in healthy humans. The ET(B) receptor seems to function as a clearance receptor and may modulate vascular tone by altering the plasma concentration of ET-1.     

Vascular areas where clonidine induces vasodilation in hypertensive and normotensive rats

The aim of this study was to find vascular areas where clonidine decreases the regional vascular resistance when this drug lowers arterial pressure in conscious spontaneously hypertensive rats and normotensive control rats. Arterial pressure was observed with an indwelling catheter at a carotid. Blood flow was measured with an electromagnetic flow probe implanted around the renal artery or the superior mesenteric artery. Regional vascular resistance was calculated as arterial pressure divided by blood flow. Intravenous bolus injection of clonidine at a dose to decrease arterial pressure decreased renal resistance and superior mesenteric resistance. Quantitatively, the combined effect of the decrease in these two resistances was enough to account for the decrease in arterial pressure. Although clonidine is thought to inhibit sympathetic nerve activity centrally, the above vasodilator effect is not ascribable to this inhibitory mechanism: Sympathetic activity to be inhibited does not seem to be present in the superior mesenteric area and clonidine similarly decreased renal vascular resistance even after renal denervation.     

Effect of nifedipine on splanchnic and pulmonary vascular capacitance

Summary. This study examines the hypothesis that nifedipine may increase splanchnic vascular capacitance and thus change the distribution of blood between the splanchnic and pulmonary circulation in heart failure patients. Relative regional blood volumes were determined by equilibrium blood pool scintigraphy during a 10 min baseline period and for 30 min after nifedipine 20 mg sublingually, with simultaneous recordings of systemic and pulmonary arterial pressures, hepatic venous wedge pressure, and cardiac output. Eight patients with ischaemic heart failure received nifedipine. Four patients served as controls. Nifedipine reduced mean arterial pressure and systemic vascular resistance in every patient. There were no significant changes in the relative blood volumes of the intestinal, hepatic, or splenic regions or in hepatic venous wedge pressure (reflecting portal venous pressure), suggesting unchanged splanchnic vascular pressure-volume relationship. Nifedipine caused a 6.3±l.0% increase in relative pulmonary blood volume and a slight increase in pulmonary vascular distending pressure from 16.1±2.9 mmHg to 17.5±2.8 mmHg (P < 0.05), suggesting that the increase in pulmonary blood volume was passively mediated. In conclusion, nifedipine did not change splanchnic vascular capacitance, but caused a small increase in pulmonary blood volume, which probably was a passive response to increased distending pressure.     

Senile pyelonephritis with the arterial hypertension syndrome: the use of trental

Eighteen patients with senile pyelonephritis and nephrogenic arterial hypertension were examined for the effect of trental monotherapy (600 mg/day) on intrarenal hemodynamics, the rate of glomerular filtration (effective renal blood flow, the intensity of blood flow in the medullary layer of the kidney), activity of the renin-angiotensin-aldosterone system (plasma renin activity, plasma and urine aldosterone), prostaglandin synthetic capacity of the kidneys (PGE and PGF2 alpha), water-electrolyte balance (circulating blood volume, sodium content in the serum and its excretion with urine), and on arterial pressure and general vascular peripheral resistance. Prolonged administration of the drug (from 3 weeks to 6 months) led to a significant improvement of the medullary blood flow, increase (p less than or equal to 0.05) of excretion of natriuretic PGE [correction of RGE] and lowering (p less than or equal to 0.05) of diurnal excretion of PGF2 alpha, which was accompanied by a rise of natriuresis (p less than or equal to 0.05) and diuresis.     

The relation between the excretion of sodium and water and the perfusion pressure in the isolated, blood-perfused, rabbit kidney, with special reference to changes occurring in clip-hypertension.

1. The sodium and water excretion rates of rabbit kidneys were studied when isolated and perfused at known pressure with blood from another normal anaesthetized rabbit. Studies at several different perfusion pressures confirmed that a small rise in perfusion pressure caused a large rise in sodium excretion and that the potential sodium-excreting ability of the isolated kidney was high. The curve obtained could be closely fitted by a quadratic equation which allowed an estimate to be made of the blood pressure below which no urine is formed, i.e. the 'theoretical perfusion pressure threshold'. For normal kidneys this was 55-4 mmHg. 2. A group of rabbits had a silver clip applied to the left renal artery and, 3-6 weeks later, the eight most hypertensive animals were selected to provide their kidneys for perfusion. Both kidneys were perfused simultaneously. The clip on the left renal artery was removed immediately before perfusion and the cannula placed distal to the stenosis in the post-stenotic dilatation. The function curves of these kidneys were compared with the curves obtained from normal kidneys. 3. The untouched kidney contralateral to the clip was found to require a significantly higher perfusion pressure (71-7 mmHg) for it to achieve a given sodium excretion rate and, surprisingly, the clipped kidney showed a similar functional change (76-4 mmHg). In other words the positions of both function curves were shifted though their slopes were not much changed. 4. Both kidneys in single-clip-hypertension appear to adapt or reset their sodium excretory behaviour. The resetting in the untouched kidney allows hypertension to be sustained without undue sodium loss. Aldosterone probably contributes little to the resetting. We infer, indirectly, that the normal kidney may, to a significant extent, restrain sodium excretion by virtue of its sympathetic innervation. We also opine that the kidney cannot be assigned fixed intrinsic functional properties on which a renal sodium-handling theory of long-term blood pressure regulation can be firmly based.     

Endovascular treatment for renal artery stenosis

Atherosclerosis accounts for 90% of the cases of renal artery stenosis. It is an important cause of secondary arterial hypertension by means of inducing the renin-angiotensin system, volume expansion, and sympathetic activation. Despite high procedural success rate of renal artery stenting, clinical trials have shown an inconsistent outcome about improvement in hypertension. The accurate predictors identify the good indication for renal artery stenting is clinically needed. Currently, the presence of hemodynamically critical stenosis causing renal ischemia, the presence of symptoms with undoubtedly benefit from revascularization, and the assessment of procedural risk are key factors for decision making about indication of renal artery stenting.     

Color Doppler sonographic appearance of renal perforating vessels in subjects with normal and impaired renal function

PURPOSE: The purpose of this study was to assess the prevalence and color Doppler sonographic characteristics of perforating vessels-small arteries and veins connecting the intrarenal vasculature with the capsular plexus-in healthy subjects, in hypertensive patients, and in patients with renal failure due to hypertensive nephroangiosclerosis or ischemic nephropathy. METHODS: Fifteen healthy subjects 24-34 years old, 15 healthy subjects 68-80 years old, 25 hypertensive patients, 25 patients with hypertension and chronic renal failure (15 mild, 10 severe), and 12 patients with hypertension and chronic renal failure and acute renal insufficiency due to ischemic nephropathy underwent color Doppler sonography of both kidneys. RESULTS: The few perforating arteries in healthy and hypertensive patients had various resistance indices and flow toward the capsule. Perforating veins in these patients were much more common than perforating arteries. Perforating arteries with a lower mean resistance index than the mean interlobar resistance index and flow toward the capsule were detected in 76% of kidneys in the patients with mild chronic renal failure and in 20% of those in patients with severe chronic renal failure. Only a few perforating veins were seen in patients with chronic renal failure. In 64% of the kidneys with renal artery stenosis detected in the patients with chronic renal failure complicated by acute renal insufficiency, there were perforating arteries with flow toward the kidney and a mean resistance index higher than the mean interlobar resistance index. CONCLUSIONS: Perforating vessels are recognizable using color Doppler sonography both in healthy subjects and in patients with renal failure. The prevalence and flow characteristics of perforating vessels differ between healthy subjects, patients with mild and with severe chronic renal failure, and patients with chronic renal failure complicated by acute renal insufficiency caused by renal artery stenosis.     

Obstructive sleep apnoea causes transient and sustained systemic hypertension

Apnoea with associated fall in arterial oxygen tension results in increased blood pressure and a striking surge in sympathetic activity, which can be measured as high catecholamine levels or increase in muscle sympathetic nerve activity. Following the termination of apnoea with resumption of breathing, sympathetic nerve activity decreases and blood pressure returns to lower values. Sympathetic mediated alternations in peripheral vascular resistance best explain these findings. Hypertension during wakefulness in untreated patients with apnoea is also associated with high sympathetic nervous system activity. Nasal continuous positive airway pressure (CPAP) has been shown to lower blood pressure in some hypertensive obstructive sleep apnoea (OSA) patients. Recently, previously untreated OSA patients exhibiting awake sympathetic hyperexcitation demonstrated striking attentuation of the response following initiation of effective CPAP therapy. Accordingly, the common problem of systemic hypertension found in untreated OSA appears to be mediated by sympathetic excitation and responds to effective CPAP therapy.     

Systemic and Renal Haemodynamics, Body Fluids and Renin in Benign Essential Hypertension with Special Reference to Natural History

Abstract. Forty patients with uncomplicated essential hypertension were investigated with respect to diurnal variability of arterial pressure (indirect recordings), intra-arterial pressure, cardiac output, plasma volume, renal plasma flow and glomerular filtration rate. Extracellular volume was estimated in 17, plasma renin concentration in 33 and vector-cardiograms were recorded in 27 patients. Treatment was discontinued at least a fortnight before and sodium intake was standardized.—Blood pressure varied across a wide range. Variability (lability) of blood pressure was quantified by expressing the difference between highest and lowest automatic blood pressure readings as a percentage of the highest reading. Cardiac output correlated with variability of blood pressure, blood volume and renal blood flow.—Plasma renin concentration was correlated with renal vascular resistance and filtration fraction.— QRS magnitude appeared to be related with the level of arterial pressure.—Haemodynamic variables exhibited a definite relationship with age, deviating in part from distribution according to age in normal populations.