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Biomedical subjects

P Hansell

Publications and source records attributed to P Hansell.

At least 19 recordsLinked to original sources
PubMed1992

Dopamine receptor blockade and synthesis inhibition during exaggerated natriuresis in spontaneously hypertensive rats.

The influence of dopamine receptor blockade and synthesis inhibition on natriuresis induced by isotonic saline volume expansion was investigated in anaesthetized spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. The aim of the study was to elucidate the mechanisms underlying the phenomenon of exaggerated natriuresis during volume expansion that has been observed in spontaneously hypertensive rats. Volume expansion, at 5% of body weight, resulted in a larger and faster natriuretic response in spontaneously hypertensive rats than in Wistar-Kyoto rats. Sixty minutes after commencement of volume expansion the natriuretic response (accumulated sodium excretion) in Wistar-Kyoto rats (n = 8) was only 24% of that in spontaneously hypertensive rats (n = 17). When spontaneously hypertensive rats were pretreated with the dopamine receptor blockers haloperidol (n = 14, 1 mg kg-1), SCH23390 (n = 8, 30 micrograms h-1 kg-1) or the dopamine synthesis inhibitor benserazide (n = 8, 50 mg kg-1; n = 5, 100 mg kg-1), the natriuretic response to volume expansion was only 16, 35, 59 and 42%, respectively, of that in untreated SHR. The corresponding proportion in the haloperidol-treated (n = 8) compared with untreated Wistar-Kyoto rats was 22%. In conclusion, isotonic volume loading results in more pronounced natriuresis in spontaneously hypertensive than in Wistar-Kyoto rats. Dopamine receptor blockade and synthesis inhibition attenuate the expansion of exaggerated natriuresis in spontaneously hypertensive rats and reduces the volume expansion natriuresis in Wistar-Kyoto rats, indicating that the dopamine system plays an important role.

Animals↗
PubMed1992

L-selectin function is required for beta 2-integrin-mediated neutrophil adhesion at physiological shear rates in vivo.

In vivo interactions between neutrophils and endothelial cells (EC) follow a multistep process involving two distinct neutrophil adhesion receptors. L-selectin, constitutively functional on resting neutrophils, mediates an activation-independent primary interaction resulting in rolling along the venular wall. Subsequent activation of rolling neutrophils induces upregulation and functional activation of beta 2-integrins (CD11/CD18) leading to firm attachment. Based on previous findings we hypothesized that, under shear force, rolling may be essential for successful neutrophil-EC recognition. Here we report results of our studies of human neutrophil behavior in interleukin (IL)-1-activated rabbit mesentery venules, an interaction that requires both L-selectin and beta 2-integrins. Rolling of human neutrophils is L-selection mediated; it was strongly reduced by monoclonal antibody inhibition or enzymatic removal of L-selectin. Furthermore, activation induced L-selectin shedding and, in a dose- and time-dependent fashion, rendered neutrophils unable to recognize inflamed EC despite expression of active beta 2-integrins, which promoted adhesion in vitro. Neutrophils activated for 5 min or longer lost most of their ability to roll. However, 1-3 min after activation, rolling was reduced (not abolished), and cells that were still able to roll displayed a significant tendency for a CD18-dependent transition from rolling to sticking. The whole sequence of events, rolling, sticking, and transendothelial migration, could be observed if an extravascular chemotactic stimulus was applied by superfusing mesenteries with leukotriene B4. Under such conditions, sticking and emigration was blocked when rolling was inhibited by enzymatic removal of L-selectin. Our results indicate that primary neutrophil interaction with inflamed EC through the L-selectin is a prerequisite for neutrophil function at physiological shear rates in vivo.

Antibodies, Monoclonal↗
PubMed1992

Effect of oxymetazoline nose drops on vascular permeability of the nasal mucosa in the rabbit after provocation with leukotriene B4.

The effects of oxymetazoline nose drops on the vascular permeability of the nasal mucosa in a provoked inflammatory reaction was studied in anesthetized rabbits. Vascular permeability (125I-albumin) was 53% higher in the leukotriene B4-provoked nostril (LTB4) compared with the vehicle-treated contralateral nostril (p < 0.05). The amount of secretions was, however, not different from the vehicle-treated side. The LTB4-induced increase in permeability was decreased by 22% when oxymetazoline was introduced (p < 0.05), and the amount of secretions was reduced by 22% (p < 0.01). The effect of oxymetazoline on the vascular permeability of the nasal mucosa can be attributed to a vascular constriction (decrease in blood flow) and/or a change in the permeability characteristics. The LTB4-induced increase in vascular permeability was not attenuated by the monoclonal antibody IB4 directed against the neutrophil adhesion complex CD11/CD18. The latter suggests that LTB4-induced vascular permeability does not require CD18-mediated neutrophil adherence in the nasal mucosa.

Administration, Intranasal↗
PubMed1992

Tubuglomerular feedback control in long-looped nephrons. Topical minireview.

The tubuloglomerular feedback mechanism is highly activated in juxtamedullary nephrons and considered to play a major role in intrarenal regulation of glomerular filtration rate. The vasculature of juxtamedullary nephrons is highly vasoreactive with a high ability for vasodilation. This vasoreactivity is a prerequisite for an important influence of the tubuloglomerular feedback mechanism on the medullary blood flow and its regulation.

Animals↗
PubMed1992

Influence of contrast media on single nephron glomerular filtration rate in rat kidney. A comparison between diatrizoate, iohexol, ioxaglate, and iotrolan.

The effects of slow (10 min) i.v. infusions of contrast media (CM, 1,600 mg I/kg b.w.) on single nephron glomerular filtration rate (SNGFR) in the rat kidney were investigated using a micropuncture technique. Diatrizoate, iohexol, or ioxaglate did not change SNGFR, although a tendency towards a transient suppression was seen during the infusion phase. Iotrolan infusion, however, decreased SNGFR (p < 0.05) and the value still remained below the control value 25 min after the start of infusion. Iotrolan is a nonionic dimeric CM and has a lower osmotic effect in the tubules than the ionic dimeric CM and the monomeric CM when given in iodine equivalent doses. These characteristics of iotrolan have probably some influence on the depression of SNGFR after iotrolan injection.

Animals↗
PubMed1991

The effect of dopamine receptor blockade on natriuresis is dependent on the degree of hypervolemia.

A number of different physiological factors and systems have been suggested to be responsible for the natriuretic effect following acute isotonic volume expansion (VE). The variation in suggestions may depend on the prevailing status of the systems governing fluid and electrolyte balance before VE, on the expansion medium and on the rate and degree of VE. A study was performed to determine whether the previously documented attenuating effect of dopamine receptor blockade on natriuresis induced by VE is dependent on the degree of hypervolemia. Anesthetized rats were pretreated with the dopamine receptor blockers haloperidol (1 mg.kg-1 body weight, i.p.), SCH 23390 (30 micrograms.hr-1.kg-1 i.v.) or vehicle and then subjected to VE at 2, 5 or 10% of body weight per hour. VE at 2, 5 and 10% increased sodium excretion in vehicle-pretreated animals 6-, 29- and 130-fold, respectively. In the haloperidol-pretreated animals the natriuretic response (accumulated sodium excretion) to VE was attenuated by 67% (P less than 0.05), 46% (P less than 0.05) and 22% (NS) at the three degrees of expansion, respectively. The corresponding attenuation in SCH 23390-treated animals were 60% (P less than 0.05), 56% (P less than 0.05) and 19% (NS), respectively. The gradual decrease in attenuation indicates that at varying degrees of hypervolemia, different physiological systems contribute differently to the renal natriuretic response. The dopamine system seems to be relatively more important in promoting natriuresis at the lower (physiological) range of hypervolemia whereas in the high range other factors have a greater impact.

Animals↗
PubMed1991

Plasma atrial natriuretic factor (alpha ANF) during hemodialysis (HD) and hemofiltration (HF).

Plasma concentrations of immunoreactive alpha ANF were measured before, during, and after 3 hours of hemodialysis (HD) and hemofiltration (HF). In seven healthy subjects plasma alpha ANF concentrations were measured to serve as controls. Highly elevated pre-treatment alpha ANF levels were obtained in the HD group (286 +/- 52 pg/ml, mean +/- SE), and in the HF group (275 +/- 48 pg/ml) as compared with the controls (40 +/- 3 pg/ml). The effect of both HD and HF on the alpha ANF concentration was not significant after the first hour of treatment. However, a significant decrease was obtained after the second (HD = 244 +/- 49, HF = 140 +/- 17) and third hours (HD = 244 +/- 48, HF = 135 +/- 15) (p less than 0.05) in both treatments. A steeper decline in the alpha ANF concentration was notable during HF compared with HD. There was a significant difference (p less than 0.05) when both modalities were compared at the end of treatment. A correlation (r2 = 0.98, p less than 0.001) was noted between changes in the alpha ANF levels and the ultrafiltration (UF) volumes only during HF. Plasma alpha ANF concentrations at the filter outlet were lower than at the inlet in both groups. It is concluded that the plasma alpha ANF concentrations are highly elevated in chronic renal failure patients. Despite the decrease in these concentrations during HD and HF it did not reach the normal plasma level. Monitoring of plasma alpha ANF may be a useful indicator for the extracellular volume status during HD and HF treatments.

Adult↗
PubMed1990

Effect of papillary exposure on intrarenal distribution of glomerular filtration rate and of plasma flow.

Removal of the renal pelvis in order to expose the renal papilla has been shown to cause impairment of the renal concentrating ability by an unknown mechanism. To study this phenomenon, urine osmolality (Uosm), single-nephron glomerular filtration rate (SNGFR) in outer and inner cortical nephrons and the inner and outer medullary plasma flow were determined. Measurements were performed on groups of rats before (control) and 15, 45 and 90 min after exposure of the left renal papilla. Rats with an intact ureter were studied in parallel to see whether the variables varied within the 90-min period of the study. In all groups of animals with an exposed papilla, Uosm was lower than in non-exposed animals. Outer cortical SNGFR in rats with exposed papillae, regardless of time, was not different from that in control rats. Inner cortical SNGFR after 45 and 90 min of exposure did not differ from that in controls, but after 15 min of exposure it was lower than in control animals. Outer and inner medullary plasma flow did not differ between rats with exposed papillae and controls, irrespective of exposure time. In conclusion, papillary exposure results in a permanent decrease in urine osmolality. This impairment of the concentrating ability cannot be attributed to prolonged changes in renal haemodynamics.

Animals↗
PubMed1990

Influence of verapamil on regional renal blood flow: a study using multichannel laser-Doppler flowmetry.

In anaesthetized male Sprague-Dawley rats the influence of the calcium entry blocker verapamil (2.4 mg h-1 kg-1, i.v.) on renal superficial cortical (CO) and outer medullary (OM) blood flow was investigated with the aim of elucidating further the intrarenal heterogeneity in vasoreactivity. The blood flow of the two regions was monitored simultaneously with a laser-Doppler flowmeter, using fibre probes with an outer diameter of 0.75 mm. One probe was directed towards the cortex and a second probe was inserted through the cortex and positioned in the outer medulla, measuring the flow within a hemisphere with a depth of 0.5-1.0 mm. The OM probe position was verified by dissecting the kidneys after each experiment. Insertion of the OM probe did not affect whole-kidney glomerular filtration rate, renal plasma flow or electrolyte excretion. Thirty minutes of verapamil infusion increased OM blood flow by 26%, but did not change CO blood flow (-1%). In spite of the increase in OM blood flow, the urine osmolality remained unaltered. Sodium excretion increased by 39%, while potassium excretion was unchanged. Mean arterial blood pressure decreased by 13%. In conclusion, this study has further supported the suggestion that the vasoreactivity is higher in the juxtamedullary than in the superficial cortical vasculature. The heterogeneity of the response is most probably due to the previously documented pressure drop along the interlobular arteries, which will create different haemodynamic conditions for the juxtamedullary and superficial afferent arterioles.

Animals↗