Does mean arterial blood pressure scale with body mass in mammals? Effects of measurement of blood pressure.

For at least the last 30 years, it has been discussed whether mean arterial blood pressure (MAP) is independent of body mass or whether it increases in accordance with the vertical height between the heart and the brain. The debate has centred on the most appropriate mathematical models for analysing allometric scaling and phylogenetic relationships; there has been previously little focus on evaluating the validity of underlying physiological data. Currently, the 2 most comprehensive scaling analyses are based on data from 47 species of mammals, based on 114 references. We reviewed all available references to determine under which physiological conditions MAP had been recorded. In 44 (38.6%) of the cited references, MAP was measured in anaesthetized animals. Data from conscious animals were reported in 59 (51.8%) of references; of these, 3 (2.6%) were radiotelemetric studies. In 5 species, data were reported from both anaesthetized and conscious animals, and the mean difference in the MAP between these settings was 20 ± 29 mm Hg. From a literature search, we identified MAP measurements performed by radiotelemetry in 11 of the 47 species included in the meta-analyses. A Bland-Altman analysis showed a bias of 1 mm Hg with 95% confidence interval (from -35 to 36 mm Hg); that is, the limits of agreement between radiotelemetric studies and studies in restrained animals were double the supposed difference in the MAP between the mouse and elephant. In conclusion, the existing literature does not provide evidence for either a positive or neutral scaling of arterial pressure to body mass across taxa.

The giraffe kidney tolerates high arterial blood pressure by high renal interstitial pressure and low glomerular filtration rate.

BACKGROUND: The tallest animal on earth, the giraffe (Giraffa camelopardalis) is endowed with a mean arterial blood pressure (MAP) twice that of other mammals. The kidneys reside at heart level and show no sign of hypertension-related damage. We hypothesized that a species-specific evolutionary adaption in the giraffe kidney allows normal for size renal haemodynamics and glomerular filtration rate (GFR) despite a MAP double that of other mammals. METHODS: Fourteen anaesthetized giraffes were instrumented with vascular and bladder catheters to measure glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). Renal interstitial hydrostatic pressure (RIHP) was assessed by inserting a needle into the medullary parenchyma. Doppler ultrasound measurements provided renal artery resistive index (RI). Hormone concentrations as well as biomechanical, structural and histological characteristics of vascular and renal tissues were determined. RESULTS: GFR averaged 342 ± 99 mL min(-1) and ERPF 1252 ± 305 mL min(-1) . RIHP varied between 45 and 140 mmHg. Renal pelvic pressure was 39 ± 2 mmHg and renal venous pressure 32 ± 4 mmHg. A valve-like structure at the junction of the renal and vena cava generated a pressure drop of 12 ± 2 mmHg. RI was 0.27. The renal capsule was durable with a calculated burst pressure of 600 mmHg. Plasma renin and AngII were 2.6 ± 0.5 mIU L(-1) and 9.1 ± 1.5 pg mL(-1) respectively. CONCLUSION: In giraffes, GFR, ERPF and RI appear much lower than expected based on body mass. A strong renal capsule supports a RIHP, which is >10-fold that of other mammals effectively reducing the net filtration pressure and protecting against the high MAP.

Selective renal vasoconstriction, exaggerated natriuresis and excretion rates of exosomic proteins in essential hypertension.

AIM: In essential hypertension (EH), the regulation of renal sodium excretion is aberrant. We hypothesized that in mild EH, (i) abnormal dynamics of plasma renin concentration (PRC) and atrial natriuretic peptide (ANP) are responsible for the exaggerated natriuresis, and (ii) exosomic protein patterns reflect the renal tubular abnormality involved in the dysregulation of sodium excretion. METHODS: After 2-week drug washout and 4-day diet, systemic and renal hemodynamics, cardio-renal hormones, glomerular filtration and renal excretion were studied in male patients during saline loading (SL). Excretion rates of exosome-related urinary proteins including apical membrane transporters were determined by proteomics-based methods. RESULTS: In patients, baseline renal vascular conductance was reduced (-44%, P < 0.001), but non-renal vascular conductances were normal while PRC was reduced and ANP elevated (both P < 0.01). SL induced exaggerated natriuresis and reduced PRC (P < 0.01), at normal suppression rate. SL increased arterial pressure in patients (+11 mmHg, P < 0.001), but not in controls; however, during time control, patients showed identical increases (+10 mmHg, P < 0.005) apparently dissociating arterial pressure from natriuresis. At baseline, excretion rates of 438 proteins ranged from 0.07 to 49.8 pmol (mmol creatinine)(-1); 12 proteins were found in all subjects, and 21 proteins were found in two or more patients, but not in controls. In patients, the excretion rate of retinoic acid-induced gene 2 protein was reduced, and excretion rates of other proteins showed increased variances compatible with pathophysiological and clinical applicability. CONCLUSION: Essential hypertension patients exhibit selective renal vasoconstriction and individually varying excretion rates of several exosome-related proteins. Hormonal changes, rather than arterial pressure, seem to cause exaggeration of natriuresis.

Study of compliance with a new, targeted antenatal D immunization prevention programme in Denmark.

BACKGROUND AND OBJECTIVES: A targeted routine antenatal anti-D prophylaxis programme was implemented in Denmark where anti-D immunoglobulin is given based on the result from noninvasive antenatal screening for fetal RHD. Our objective was to evaluate compliance with this new programme right after its initiation. MATERIALS AND METHODS: We examined the treatment outcome of 239 D-negative pregnant women who gave birth at our hospital between June and September 2010. RESULTS: The majority of these women (90%) underwent antenatal RHD screening, 86% of the women who were recommended antenatal prophylaxis received anti-D, and 99% of the women who delivered RhD-positive infants received postnatal anti-D. CONCLUSION: These compliance results are acceptable as they were obtained only a few months after the initiation of the new prophylaxis regime. However, suggestions to further improve compliance are presented.

Renal cortical and medullary blood flow during modest saline loading in humans.

AIM: Renal medullary blood flow (RMBF) is considered an important element of sodium homeostasis, but the experimental evidence is incongruent. Studies in anaesthetized animals generally support the concept in contrast to measurements in conscious animals. We hypothesized that saline-induced natriuresis is associated with changes in RMBF in humans. METHODS: After 4 days of low-sodium diet, healthy men were subjected to slow intravenous saline loading (12 µmol kg(-1) min(-1)) for 4 h. Renal medullary and cortical blood flow was determined by positron emission tomography with H(2)(15)O before and after saline infusion using two independent imaging processing methods. One based on a previously published algorithm (voxel peeling) and a novel method based on contrast-enhanced computed tomography (CT). Blood pressure was measured oscillometrically every 10 min. Cardiac output, heart rate and total peripheral resistance were recorded continuously. RESULTS: Saline loading increased the urinary sodium excretion by 3.6-fold (21-76 µmol min(-1) , P < 0.01). The RMBF was 2.6 ± 0.2 mL g(-1) tissue min(-1) before and 2.7 ± 0.1 mL g(-1) tissue min(-1) after saline (n.s.). Cortical blood flow was 3.6 ± 0.1 before and 3.4 ± 0.2 after saline (n.s.). Mean arterial blood pressure did not change measurably (90 vs. 90 mmHg). Bland-Altman analysis suggested agreement between results obtained with voxel peeling (2.6 ± 0.2 mL g(-1) tissue min(-1)) and contrast-enhanced CT (2.0 ± 0.1 mL g(-1) tissue min(-1)). CONCLUSION: In normal humans, changes in RMBF are not necessarily involved in the natriuretic response to modest saline loading. This result is in line with data from conscious rodents.

Dexamethasone suppression test in depressive stroke patients.

Depressive psychiatric patients often shown non-suppression to the dexamethasone suppression test (DST). Stroke patients shows a high frequency of depression. In the present study the DST was studied in 76 stroke patients and 26 controls. No difference was found in frequency of non-suppression to the DST between depressive and non-depressive stroke patients. It was found that postdexamethasone plasma cortisol level at 08 a.m. was significantly higher in patient with the lesion in the right hemisphere compared to patients with the lesion in the left hemisphere.

Bartter's syndrome--treatment with potassium, spironolactone and ACE-inhibitor.

The treatment of Bartter's syndrome is fraught with difficulties, and there is no consensus concerning the pathogenetic mechanisms involved. Potassium depletion with hypokaliaemia is a dominant feature of the syndrome. In this case history, a 42-year-old woman suffering from Bartter's syndrome did not improve on several therapeutic trials. An impressive progress was noted, however, after intensive potassium repletion with subsequent potassium/spironolactone/ACE-inhibitor treatment. After 24 months her condition was unchanged with normal and stable Se-potassium concentration.

The renin-angiotensin system and kidney function during initial insulin treatment in diabetic man.

Glomerular filtration rate, renal plasma flow, active renin, renin substrate and angiotensin II concentrations were monitored in nine consecutive patients (3 women, 6 men, mean age 31 years) with newly diagnosed, insulin-dependent diabetes. Measurements were performed before and during the initial eight days of intensive insulin treatment. All patients had ketonuria but none had acidosis. Glomerular filtration rate and renal plasma flow were significantly increased at the time of diagnosis as compared with values from normal subjects. A highly significant decline in glomerular filtration rate from 160 +/- 9 (SEM) to 133 +/- 5 ml/min x 1.73 m2 was seen during the initial eight days of treatment (p less than 0.01). Likewise renal plasma flow declined from 601 +/- 33 to 558 +/- 35 ml/min x 1.73 m2 (p less than 0.05). Plasma concentration of renin was within normal range at day 0, and remained unchanged during the eight day study. Also renin substrate concentration was normal and unchanged during the observation period, whereas angiotensin II concentration was low and unchanged. Our study does not support the suggestion that the renin-angiotensin system contributes to the hyperfiltration characteristically found in newly diagnosed insulin-dependent diabetic patients.

Metabolic and cardiovascular responses to epinephrine in diabetic autonomic neuropathy.

Norepinephrine-induced vasoconstriction, which is mediated by alpha-adrenergic receptors, is accentuated in patients with autonomic neuropathy. In contrast, responses mediated by beta-adrenergic receptors, including vasodilatation and metabolic changes, have not been evaluated in these patients. To study these responses, we administered epinephrine in a graded intravenous infusion (0.5 to 5 micrograms per minute) to seven diabetic patients without neuropathy, seven diabetic patients with autonomic neuropathy, and seven normal subjects. Mean arterial pressure decreased significantly in the patients with autonomic neuropathy (P less than 0.01) but was unchanged in the other groups. Since cardiac output increased to a similar extent in the three groups, the decrease in blood pressure was due to a significantly larger decrease (P less than 0.01) in total peripheral vascular resistance in the patients with autonomic neuropathy. The heart rate increased significantly more during the infusions in the patients with neuropathy than in those without neuropathy. Epinephrine produced a greater increase in blood glucose, the glucose-appearance rate, lactate, glycerol, and free fatty acids in the patients with autonomic neuropathy than in the other groups (P less than 0.05). These findings indicate that several beta-receptor-mediated responses to epinephrine are enhanced in patients with diabetic autonomic neuropathy. The underlying mechanism remains to be elucidated.

Partial purification of human renin substrate.

A two-step purification method is described for the preparation of renin substrate from human plasma. Pooled plasma from women on oral contraceptives is used for the purification. The overall yield of renin substrate is 57%, with a twenty-fold purification. The specific renin substrate content of the preparation, as determined by enzymatic degradation with an excess of human renin, is 2 mug angiotensin I per mg protein. The product has a very low endogenous renin activity and is free from angiotensinase activity. An additional purification step involving affinity chromatography is described. In pilot studies a renin substrate yield of 37% has been achieved, with a hundred-fold purification. The final product has a specific renin substrate content of 10 mug angiotensin I per mg protein. The preparation contains up to 12 different plasma proteins, nine of which have been identified and quantitated.