Long-term control of arterial blood pressure.

Two concepts for the long-term regulation of arterial pressure were considered in this review, the neural control hypothesis and the volume regulation hypothesis. The role of the nervous system and fluid volume regulation are intertwined in a way that has made it difficult to experimentally evaluate their separate contributions in the long-term regulation of arterial pressure. Nevertheless, from a substantial body of work related to the neural control of cardiovascular function, it appears that the ability of the nervous system to control arterial pressure is limited to the detection and correction of rapid short-term changes of arterial pressure. A long and exhaustive search has yet yielded no new neural mechanisms beyond the classic sinoaortic baroreceptors that can detect changes of arterial pressure. The baroreceptor mechanisms are of great importance for the moment-to-moment stabilization of arterial pressure, but because they do not possess sufficient strength and because they reset in time to the prevailing level of arterial pressure, they cannot provide a sustained negative feedback signal to provide long-term regulation of arterial pressure in face of sustained stimuli. This is not to say that the nervous system cannot affect the long-term level of arterial pressure. A distinction is made here between the many factors that can influence the long-term level of pressure and those that actually serve to detect changes of pressure and serve to maintain the level of pressure within a narrow range over the period of our adult lifetime. In this sense, there is evidence that in genetically susceptible individuals, environmental stresses can influence the long-term level of arterial pressure via the central and peripheral neural autonomic pathways. It is inappropriate, however, to view the nervous system as a long-term controller of arterial pressure because there is yet no evidence that the CNS can detect changes of arterial pressure nor changes in total body sodium and water content over sustained periods whereby it could provide an adequate long-term normalization of such error signals. In contrast, evidence has grown in support of the renal pressure-diuresis volume regulation hypothesis for the long-term control of arterial pressure over the past decade. An enhanced understanding of the mechanisms of pressure diuresis-natriuresis coupled with studies exploring how changes of vascular volume can influence vascular smooth muscle tone provide a compelling basis for this hypothesis of long-term arterial pressure regulation. This overall concept is represented and summarized in Figure 12.(ABSTRACT TRUNCATED AT 400 WORDS)     

Renal hemodynamics and blood pressure control in patients with pyelonephritic renal scarring

Pyelonephritic renal scarring is a common cause of renal failure and hypertension. We studied glomerular filtration rate (GFR), renal plasma flow (RPF), filtration fraction (FF), total renal area (TRA), systolic (SBP) and diastolic (DBP) blood pressure in 22 female patients with verified renal scarring and a history of febrile urinary tract infection (UTI) and in 9 healthy age-matched women with normal urograms and no history of symptomatic UTI. The patients with renal scarring had significantly lower GFR, smaller TRA and higher SBP than the healthy controls, but not significantly different RPF or FF. A decrease in GFR and RPF was associated with higher SBP and DBP in the patients with renal scarring. RPF/TRA, representing an approximation of the perfusion of renal tissue and GFR/TRA, were similar in patients with renal scarring and healthy controls. A reduction of renal parenchyma was accompanied by a proportional decrease in GFR and RPF, resulting in unchanged FF. These findings do not support the concept of hyperfiltration as a main cause of renal insufficiency in patients with pyelonephritis renal scarring. An increase in FF and a decrease in GFR/TRA and RPF/TRA was associated with higher DBP and a decrease in GFR/TRA and RPF/TRA with an increase in the urinary albumin excretion. We conclude that renal hemodynamics play an important part in the blood pressure control of patients with renal scarring and that in these patients with various degrees of renal failure there was no evidence of hyperfiltration or hyperperfusion by remnant glomeruli.     

Zinc supplementation prevents alcoholic liver injury in mice through attenuation of oxidative stress

Alcoholic liver disease is associated with zinc decrease in the liver. Therefore, we examined whether dietary zinc supplementation could provide protection from alcoholic liver injury. Metallothionein-knockout and wild-type 129/Sv mice were pair-fed an ethanol-containing liquid diet for 12 weeks, and the effects of zinc supplementation on ethanol-induced liver injury were analyzed. Zinc supplementation attenuated ethanol-induced hepatic zinc depletion and liver injury as measured by histopathological and ultrastructural changes, serum alanine transferase activity, and hepatic tumor necrosis factor-alpha in both metallothionein-knockout and wild-type mice, indicating a metallothionein-independent zinc protection. Zinc supplementation inhibited accumulation of reactive oxygen species, as indicated by dihydroethidium fluorescence, and the consequent oxidative damage, as assessed by immunohistochemical detection of 4-hydroxynonenal and nitrotyrosine and quantitative analysis of malondialdehyde and protein carbonyl in the liver. Zinc supplementation suppressed ethanol-elevated cytochrome P450 2E1 activity but increased the activity of alcohol dehydrogenase in the liver, without affecting the rate of blood ethanol elimination. Zinc supplementation also prevented ethanol-induced decreases in glutathione concentration and glutathione peroxidase activity and increased glutathione reductase activity in the liver. In conclusion, zinc supplementation prevents alcoholic liver injury in an metallothionein-independent manner by inhibiting the generation of reactive oxygen species (P450 2E1) and enhancing the activity of antioxidant pathways.     

Role of hypervolemia and renin in the blood pressure control of patients with pyelonephritis renal scarring

Patients with pyelonephritic renal scarring are at risk of developing renal failure and hypertension. We studied glomerular filtration rate (GFR), renal plasma flow (RPF), filtration fraction (FF), systolic (SBP) and diastolic (DBP) blood pressure, fractional sodium, potassium and phosphate excretion, peripheral renin activity (PRA), plasma aldosterone (p-Aldo), urinary albumin excretion (U-Alb) and urinary beta 2-microglobulin excretion (beta 2-M) in hydropenia and during transition to 3% volume expansion with isotonic saline infusion in 22 female patients with renal scarring due to pyelonephritis and 9 healthy controls. The patients had significantly lower GFR, higher SBP and higher PRA in hydropenia, but there was no significant difference in RPF, FF, DBP or p-Aldo. After volume expansion, SBP, DBP, PRA and p-Aldo were significantly higher in patients than in controls. Transition to 3% volume expansion was associated with a similar increase in SBP in both patients and controls, whereas DBP increased significantly more in the patients (p less than 0.01). Volume expansion resulted in a significant suppression of PRA and p-Aldo in both patients and controls. The patients with renal scarring had the same capacity to excrete sodium and water during transition to volume expansion as the healthy controls. The renin-aldosterone system seems abnormally activated and is probably more important than hypervolemia in the development of hypertension in this group of patients.     

Metabolic and blood pressure monitoring in diabetic renal failure

In a prospective study of eight patients with type I diabetic renal failure, metabolic and blood pressure monitoring was evaluated during progression to end-stage renal disease (ESRD). The mean observation time was 37 months. The mean glomerular filtration rate (GFR) fell significantly (from 33 to 16 ml/min) implying a mean deterioration rate of 0.57 ml/min/month. This rate showed significant correlation with mean arterial blood pressure at out-patient observations, but not with blood glucose monitored as 24-hour profile or with glycosylated hemoglobin. Patients with growth hormone values within the upper limit of the normal range showed faster decline of GFR than patients with low values. The study demonstrated that advanced diabetic renal failure may progress slowly to ESRD. The blood pressure pattern, but not blood glucose values, influenced significantly the deterioration rate of glomerular function.     

Receptors for angiotensins I and II: their relevance to renal haemodynamics, blood pressure control and hind-limb blood flow.

The well established differential pulmonary handling of angiotensins I and II indicates the possibility that vascular receptors for the deca- and octa-peptides do not necessarily involve common sites in the renal vasculature either. Experimental findings involving haemodynamic changes within the kidney in anaesthetised and conscious sheep, with utilization of the angiotensins, and also of noradrenaline, are briefly presented; the implications of the intra-renal water and creatinine transfers are discussed, especially as they concern the possible location of angiotensin receptors in the renal blood vessels. Other aspects of the relationships between the peptides are also taken into account particularly with regard to a postulated angiotensin I [NaCl] dependent peritubular capillary antidiuretic action, angiotensin converting enzyme inhibition, Goldblatt clamp induced hypertension and blood flow through the hind-limbs.     

Long-term reproducibility of ambulatory blood pressure in unselected elderly subjects.

The aim of this study was to evaluate the long-term reproducibility and validity of 24-h ambulatory blood pressure measurements (ABPM) in an unselected elderly population. In a rural Finnish community 503 randomly chosen invited persons over 65 years of age participated and went through 24-h ABPM. As part of the validation of the methodology, the reproducibility study was conducted in 26 persons (age 65-76 years). Two identical sets of measurement were performed at 4-12 (median 8) month intervals. The agreement between measurements was assessed by correlation coefficients and standard deviation (SD) of the differences. There were no significant differences in 24-h, daytime and night-time average diastolic blood pressure (DBP) and daytime average systolic blood pressure (SBP) between the two measurements. During the second measurement, 24-h SBP and night-time average SBP were slightly higher than those obtained by the first monitoring. Average 24-h SBP and DBP were 18 and 7 mmHg lower, respectively, than office blood pressure averages. The correlation coefficients were significantly higher for 24-h ambulatory blood pressure than for office blood pressure. The SD of the mean difference between visits was significantly lower for 24-h ambulatory blood pressure than for office blood pressure measurements. These findings show that the long-term reproducibility of ambulatory blood pressure is good in an elderly unselected population and better than the office blood pressure reproducibility.     

Long-term consequences of cis-platinum-induced renal injury: A structural and functional study

Previous studies have shown that a single dose of the antitumor drug, cis-platinum, causes renal cyst formation in rats 1–6 months after drug injection. This observation led to a further evaluation of the long-term effects of cisplatinum on the kidney of the rat. Fisher 344 rats (N = 13) were given either a single intraperitoneal injection of cis-platinum (6 mg/kg body weight) or saline (control) and 15 months later renal function and pathology were assessed. The glomerular filtration rate and urinary osmolality in the cis-platinum-treated rats at 15 months were significantly reduced compared to controls, 520 ± 59 μl/min/gm kidney weight versus 799 ± 100 (P < .05) and 871 ± 194 mOsm/kg H₂O versus 1471 ± 162 (P < .05), respectively. Renal injury was less marked and of a more chronic type than to that originally described 6 months after cis-platinum. Morphometric evaluation of renal injury revealed cis-platinum-treated rats had greater numbers of abnormal proximal tubules (atrophic or hyperplastic) when compared to control rats. Glomerular sclerosis and interstitial fibrosis were also more prevalent in the animals injected with cis-platinum. In the inner stripe of the outer medulla, numerous markedly dilated tubules filled with hyaline casts and lined by simple squamous cells were present. To assess why cis-platinum exerts a chronic effect on the kidney, total platinum levels were measured in different regions of the kidney as a function of time after drug injection. Platinum levels were significantly elevated in the cortex, outer and inner stripe regions, and in the inner medulla for as long as 1 month after cis-platinum treatment. By 2 months, however, the values were no greater than controls. In summary, cis-platinum exerts a significant long-term chronic effect on the structure and function of the rat kidney.     

Baroreceptors and the long-term control of blood pressure

The current consensus is that arterial baroreceptors are vitally important in the short term (seconds to minutes) control of mean arterial pressure (MAP) but are unimportant in determining the long-term level of MAP. The latter statement is based primarily on two observations: first, that baroreceptors rapidly reset to the prevailing level of MAP and second, that total baroreceptor denervation has no lasting effect on the average daily MAP, although the variability of MAP is increased dramatically. However, recent studies in intact experimental animals have produced results that suggest baroreceptor resetting may not be as rapid or complete as previously thought. Furthermore, reconsideration of the responses to baroreceptor denervation suggest that the condition may accurately represent responses to short-term baroreceptor unloading but not long-term unloading. Results obtained using a new model of chronic baroreceptor unloading indicate that the condition results in a sustained increase in MAP. These results strongly suggest that the role of baroreceptors in the long term control of MAP needs to be revisited.     

The relationship of diet to blood pressure control

Sodium restriction has become an integral part of the medical management of hypertension. In general the degree of sodium restriction recommended by physicians depends upon the severity of the disease. The commonly prescribed sodium restricted diets are classified as mild and moderate. Mild sodium restriction refers to a diet in which 3.0-4.0 gm of sodium are allowed per day. Moderate sodium restriction is indicated when hypertension is more severe; 1-2 gm of sodium are allowed daily. Sodium added in the processing of foods contributes significantly to the sodium content of the diet. “Convenience” and “fast” foods are high in sodium and are not allowed the hypertensive patients. Significant advances have occurred in the past decade in the medical management of hypertension. The sodium-restricted diet remains the cornerstone of effective blood pressure control. Therefore, nutrition must become an integral part of the hypertensive treatment program.     

An Angiotensin-converting enzyme inhibitor, zofenopril, prevents renal ischemia/reperfusion injury in rats

Zofenopril ameliorates experimental cardiac ischemia/reperfusion (IR) injury in animal models and exhibits beneficial cardiovascular effects in patients with myocardial infarction. The objective of the present research was to investigate whether zofenopril can protect against renal IR injury. Rats were divided into 4 experimental groups: (a) control, (b) IR (60 min of ischemia followed by 24 hr of reperfusion), (c) zofenopril (15 mg/kg/day for 2 days), and (d) zofenopril+IR. All of the rats underwent right nephrectomy, and the rats in the IR and zofenopril+IR groups also underwent IR.then the left kidneys were removed for biochemical analyses and microscopic examination. There were no abnormalities in the biochemical and microscopic findings in the preoperative right kidneys. The lipid peroxidation, protein oxidation, and nitric oxide levels as well as xanthine oxidase and myeloperoxidase activities were increased and the catalase and superoxide dismutase activities were decreased in the IR group; zofenopril treatment prevented these changes (p <0.05). In the IR group, the kidney sections showed severe acute tubular damage including brush border loss, nuclear condensation, cytoplasmic swelling, and loss of nuclei; in the zofenopril+IR group, the normal glomerular morphology was preserved and there was slight edema of the tubular cells. The renal damage score was significantly reduced in the zofenopril+IR group vs the IR group (p <0.05).In conclusion, IR injury caused oxidative damage in renal tissue and zofenopril prevented this IR injury.     

Long-term ambulatory monitoring of indirect arterial blood pressure using a volume-oscillometric method

A new portable instrument equipped with a microprocessor was designed for the long-term ambulatory monitoring of indirect arterial pressure in the human finger at desired intervals using a volume-oscillometric technique. All the necessary procedures such as (1) programmed control of cuff pressure, (2) detection of the systolic end-point and the point of maximum amplitude of arterial volume pulsations, (3) reading of the cuff pressures corresponding to these two points, (4) its processing and (5) recording of the systolic and mean pressure together with heart rate on a digital memory integrated circuit were performed automatically. After the monitoring, the data were reproduced and analysed by a conventional personal computer. Simultaneous comparison of the data with direct measurement, operation and evaluation of this instrument, and ambulatory monitoring were carried out. With this instrument noninvasive and accurate monitoring of arterial pressure could be made in unrestricted subjects during daily activities.