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.

Impaired myogenic tone in isolated cerebral and coronary resistance arteries from the goto-kakizaki rat model of type 2 diabetes.

AIM: Type 2 diabetes is associated with stroke and cardiac dysfunction. We therefore investigated isolated middle cerebral arteries and coronary septal arteries from the diabetic Goto-Kakizaki (GK) rat model of nonobese type 2 diabetes. METHODS: Myogenic tone and agonist-induced responses were investigated under isobaric conditions with simultaneous recording of [Ca2+]i. Rho-kinase and NO pathways were investigated using specific pharmacological tools. RESULTS: Arteries from GK rats developed less tone at pressures from 20 to 100 mm Hg than arteries from control Wistar (CW) rats while [Ca2+]i was similar. Blocking the Rho-kinase pathway decreased the pressure-induced development of tone and after blockade no difference in myogenic tone between arteries from GK and CW rats was seen. Cerebral arteries had similar tone to a maximal concentration of U46619 (GK: 35.5±2% vs. CW: 31.6±5%), while coronary arteries from GK rats developed less tone than arteries from CW rats (12±3 vs. 26.1±3%). Endothelium-dependent vasodilation to A23187 (cerebral) and to acetylcholine (coronary) was not different between arteries from GK and CW rats. CONCLUSION: Our data suggest that in resistance arteries from the brain and the heart of GK rats the myogenic tone is decreased due to impaired calcium sensitivity likely due to a defective Rho-kinase pathway.

NS309 restores EDHF-type relaxation in mesenteric small arteries from type 2 diabetic ZDF rats.

BACKGROUND AND PURPOSE: The endothelium-derived hyperpolarizing factor (EDHF)-type relaxation in mesenteric small arteries from 21 week old Zucker lean (ZL) and Zucker diabetic fatty (ZDF) rats was investigated using (6,7-dichloro-1H-indole-2,3-dione 3-oxime) (NS309), a potent activator of small-conductance, calcium-activated potassium channel (SK(Ca)) and intermediate-conductance, calcium-activated potassium channel (IK(Ca)). EXPERIMENTAL APPROACH: In the presence of inhibitors of cyclooxygenase and nitric oxide synthase [indomethacin and N(omega)-nitro-L-arginine methyl ester (l-NAME), respectively], acetylcholine (ACh)-induced hyperpolarization and EDHF-type relaxation were investigated under isometric conditions in the wire myograph using 0.5 and 1 microM NS309 and/or selective blockers of SK(Ca) and IK(Ca) channels. Membrane potential was recorded with glass microelectrodes, and changes in the intracellular calcium concentration of endothelial cells were visualized by confocal microscopy. SK(Ca) expression was assessed by Western blotting. KEY RESULTS: In arteries from ZDF rats, ACh-induced relaxation and membrane hyperpolarization were attenuated and, compared with arteries from ZL rats, NS309 was less potent at causing relaxation. Incubation with 0.5 microM NS309 did not increase ACh-induced relaxation in arteries from ZDF rats significantly. However, 1 microM NS309 restored it (both in the absence and in the presence of indomethacin and l-NAME) without changing endothelial intracellular calcium concentration. The restored EDHF-type relaxation was more sensitive to TRAM-34 (1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole) (1 microM) than to apamin. Expression of the SK(Ca) channel was unaltered. CONCLUSIONS AND IMPLICATIONS: The attenuated EDHF-type relaxation in mesenteric small arteries from ZDF rats can be restored by NS309 without changes in the intracellular calcium concentration of endothelial cells. These results may have clinical implications for the treatment of endothelial dysfunction in overweight type 2 diabetic patients.

Jugular venous pooling during lowering of the head affects blood pressure of the anesthetized giraffe.

How blood flow and pressure to the giraffe's brain are regulated when drinking remains debated. We measured simultaneous blood flow, pressure, and cross-sectional area in the carotid artery and jugular vein of five anesthetized and spontaneously breathing giraffes. The giraffes were suspended in the upright position so that we could lower the head. In the upright position, mean arterial pressure (MAP) was 193 +/- 11 mmHg (mean +/- SE), carotid flow was 0.7 +/- 0.2 l/min, and carotid cross-sectional area was 0.85 +/- 0.04 cm(2). Central venous pressure (CVP) was 4 +/- 2 mmHg, jugular flow was 0.7 +/- 0.2 l/min, and jugular cross-sectional area was 0.14 +/- 0.04 cm(2) (n = 4). Carotid arterial and jugular venous pressures at head level were 118 +/- 9 and -7 +/- 4 mmHg, respectively. When the head was lowered, MAP decreased to 131 +/- 13 mmHg, while carotid cross-sectional area and flow remained unchanged. Cardiac output was reduced by 30%, CVP decreased to -1 +/- 2 mmHg (P < 0.01), and jugular flow ceased as the jugular cross-sectional area increased to 3.2 +/- 0.6 cm(2) (P < 0.01), corresponding to accumulation of approximately 1.2 l of blood in the veins. When the head was raised, the jugular veins collapsed and blood was returned to the central circulation, and CVP and cardiac output were restored. The results demonstrate that in the upright-positioned, anesthetized giraffe cerebral blood flow is governed by arterial pressure without support of a siphon mechanism and that when the head is lowered, blood accumulates in the vein, affecting MAP.

Increased contractility to noradrenaline and normal endothelial function in mesenteric small arteries from the Goto-Kakizaki rat model of type 2 diabetes.

UNLABELLED: Type 2 diabetes is associated with many circulatory manifestations, including alteration in endothelial function and hypertension. In this study we investigate the morphology and contractile response as well as the endothelial function of resistance arteries from the spontaneously diabetic Goto-Kakizaki (GK) rat, a model of lean type 2 diabetes expressing glucose intolerance. METHODS: Isolated mesenteric small arteries were investigated under isometric conditions in a wire myograph system using noradrenaline (NA) and the endothelium-dependent vasorelaxant acetylcholine (ACh). Media thickness was measured and media lumen ratio calculated. RESULTS: No apparent morphological difference was noted between the arteries from GK rats and control Wistar (CW) rats. When exposed to the maximal NA concentration used (30 microM), arteries from GK rats developed significantly more tension than arteries from CW rats. In the presence of indomethacin (a specific blocker of the COX synthase) and of L-NAME (an inhibitor of eNOS), the response to NA was still significantly greater in GK rat arteries. Under control conditions, arteries from both groups showed intact relaxation to ACh. After incubation with indomethacin and L-NAME, both groups showed a non-NO nonprostaglandin-dependent relaxation to ACh. This relaxation could be blocked by a combination of apamin and charybdotoxin. CONCLUSION: This study shows that mesenteric small arteries from the diabetic GK rat have increased contractile response to NA, along with a normal endothelial function and unaltered morphology.

Rehabilitation in COPD: the long-term effect of a supervised 7-week program succeeded by a self-monitored walking program.

Pulmonary rehabilitation in chronic obstructive pulmonary disease (COPD) improves exercise tolerance and health status, however, these effects have been shown to decline after termination of the rehabilitation program. This study has examined the long-term effect of a 7-week supervised rehabilitation program combined with daily self-monitored training at home on exercise tolerance and health status. Two hundred and nine consecutive COPD patients who had completed a 7-week pulmonary rehabilitation program were assessed with endurance shuttle walk test (ESWT) and the St George's Respiratory Questionnaire (SGRQ) at baseline, 0, 3, and 12 months after the program. Sixty-eight (32.5%) patients did not attend the 1-year follow-up. Among the 141 patients who competed the 1-year evaluation, the initial improvement after the 7-week program in the ESWT time was 180 s or 101% (p = 0.001) and in SGRQ 3.4 units (p = 0.001). These effects were maintained at the 1-year evaluation (ESWT 59% above baseline; p < 0.001 and improved SGRQ 3.0 units compared with baseline; p = 0.011). The 31 patients who attended the 6-month, but not the 12-month evaluation, improved ESWT time by 96 s (p = 0.02) without any change in SGRQ +2.0 (p = 0.40). A relative simple and inexpensive 7-week supervised rehabilitation program combined with daily self-monitored training at home was able to maintain significant improvement in exercise tolerance and health status throughout 1 year. Death and hospital admissions due to acute exacerbations were the main reasons for non-attendance in the follow-up period.

Risk factors for rehospitalisation in COPD: role of health status, anxiety and depression.

The aim of the present study was to analyse the risk of rehospitalisation in patients with chronic obstructive pulmonary disease and associated risk factors. This prospective study included 416 patients from a university hospital in each of the five Nordic countries. Data included demographic information, spirometry, comorbidity and 12 month follow-up for 406 patients. The hospital anxiety and depression scale and St. George's Respiratory Questionnaire (SGRQ) were applied to all patients. The number of patients that had a re-admission within 12 months was 246 (60.6%). Patients that had a re-admission had lower lung function and health status. A low forced expiratory volume in one second (FEV1) and health status were independent predictors for re-admission. Hazard ratio (HR; 95% CI) was 0.82 (0.74-0.90) per 10% increase of the predicted FEV1 and 1.06 (1.02-1.10) per 4 units increase in total SGRQ score. The risk of rehospitalisation was also increased in subjects with anxiety (HR 1.76 (1.16-2.68)) and in subjects with low health status (total SGRQ score >60 units). When comparing the different subscales in the SGRQ, the closest relation between the risk of rehospitalisation was seen with the activity scale (HR 1.07 (1.03-1.11) per 4 unit increase). In patients with low health status, anxiety is an important risk factor for rehospitalisation. This may be important for patient treatment and warrants further studies.

Functional abnormalities in isolated arteries from Goto-Kakizaki and streptozotocin-treated diabetic rat models.

Several different rat models have been developed for both type 1 and type 2 diabetes with the aim of displaying specific traits of diabetes. For example, a review on nephropathy associated with type 2 diabetes included 16 different rodent models ; new models are still being developed. The large number of different models developed for different traits makes it difficult to choose the right model for a given study. It is often a problem that the models are not sufficiently characterized, which makes it easy to misinterpret data or even come to the wrong conclusions. In this brief review, we will concentrate on the functional responses obtained in vitro from mesenteric arteries and aortic segments from rat models of diabetes. Since it is beyond the scope of this review to overview all different rodent models of diabetes, we will focus on two commonly used models of diabetes, namely the streptozotocin (STZ)-induced type 1 diabetic rat model and the inbred type 2 diabetic Goto-Kakizaki (GK)-rat model.

[Rehabilitation of patients with chronic obstructive lung disease. Are two exercise sessions per week sufficient?]. / Rehabilitering af patienter med kronisk obstruktiv lungesygdom. Er troening to gange ugentlig tilstroekkeligt?

Several studies of patients with chronic obstructive pulmonary disease (COPD) have shown that pulmonary rehabilitation three to seven times a week improves exercise performance and well being. This study investigates feasibility, effect and economic aspects of a programme consisting of two sessions a week. Twenty-four patients were randomized to rehabilitation and twenty-one to placebo. In an outpatient setting patients were assigned to an eight-week programme of exercise plus education twice a week (Exercise group) or conventional community cares (Placebo group). Seven patients did not complete the rehabilitation. The characteristics of the thirty-eight COPD patients at baseline (mean +/- SD): forced expiratory volume in one second (FEV-1) 1.1 +/- 0.4 L, six-minute walk distance (6MWD) 413 +/- 75 m. Rehabilitation resulted in an insignificant improvement in well being and the 6MWD (29 m ¿95% confidence interval: -8-66 m¿. Rehabilitation session twice a week for eight weeks had no effect in patients with moderate COPD.