Changes in cerebral blood flow (CBF), in chloralose-anaesthetized spontaneously hypertensive rats, were measured simultaneously with the hydrogen clearance (HC) method and laser Doppler flowmetry (LDFM) in order to examine the correlation between results obtained with the two techniques. To induce changes in CBF the rats were bled and CBF measured at different levels of mean arterial pressure. As would be expected, with the platinum electrode at the depth of about 1 mm in the somatosensory cortex, HC gave biexponential curves reflecting clearance in two distinct compartments. During control situation the HC method gave the following values (mean +/- SE, n = 20, ml min-1 100 g-1): fast (fCBF) 158.6 +/- 11.5, slow (sCBF) 29.1 +/- 1.6 with a weighted mean flow (mCBF) of 83.3 +/- 7.4. These fCBF and sCBF values correspond well to those of others obtained with [14C]iodoantipyrine autoradiography in the cerebral cortex and corpus callosum, and better than the results of other studies using HC in rats. Our results, comparing data from HC and LDFM, show a linear relationship between relative values of blood flow changes, the coefficients being 0.658, 0.876 and 0.878 for the correlation between the LDFM data and relative changes in fCBF, sCBF and mCBF, respectively. All three regression lines were significantly different from the line of identity. Much of the discrepancy between the two methods may be related to limitations inherent in each of them, despite efforts to minimize their effects. Thus the depth sensitivity of LDFM in the brain may be greater than expected. In conclusion, the laser Doppler method seems, nevertheless, to be most useful for continuous estimations of changes in cerebral blood flow.

Resting human sympathetic vasoconstrictor traffic displays large reproducible inter‐individual differences which are similar in nerves to muscle, heart and kidney. In spite of this there is no correlation between levels of blood pressure and sympathetic traffic. To test the hypothesis that the pressor effect of the vasoconstrictor activity is counteracted by a circulating dilating factor we measured muscle nerve sympathetic activity (MSA) and an indicator of nitric oxide release (plasma nitrate) in healthy young males. Sympathetic activity was recorded with the microneurographic technique in the peroneal nerve and a forearm venous plasma sample was obtained in twenty‐one normotensive males aged 21–28 years. Plasma nitrate was analysed by gas chromatography and mass spectrometry. There was a positive linear correlation between the plasma nitrate concentration and the strength of MSA both when the nerve activity was expressed as bursts per minute and bursts per 100 heart beats (r= 0.51, P= 0.02 and r= 0.46, P= 0.04, respectively). The data suggest that the stronger the sympathetic activity the higher the release of the dilating substance, nitric oxide. This would be expected to counteract vasoconstrictor effects of the nerve traffic and thereby contribute to the lack of relationship between resting levels of MSA and blood pressure. We speculate that altered coupling between sympathetic traffic and nitric oxide release may cause abnormal peripheral resistance, e.g. in hypertension.

1 We designed and synthesized several novel cyclic MSH analogues and tested their a nities for cells expressing the MC1, MC3, MC4 and MC5 receptors. 2 One of the substances HS028 (cyclic [AcCys 11 , dichloro-D-phenylalanine 14 , Cys 18 , Asp-NH 2 22 ]-b-MSH 11 ± 22 ) showed high a nity (Ki of 0.95nM) and high (80 fold) MC4 receptor selectivity over the MC3 receptor. HS028 thus shows both higher a nity and higher selectivity for the MC4 receptor compared to the earlier ®rst described MC4 receptor selective substance HS014. 3 HS028 antagonised a a-MSH induced increase in cyclic AMP production in transfected cells expressing the MC3 and MC4 receptors, whereas it seemed to be a partial agonist for the MC1 and MC5 receptors. 4 Chronic intracerebroventricularly (i.c.v.) administration of HS028 by osmotic minipumps signi®cantly increased both food intake and body weight in a dose dependent manner without tachyphylaxis for a period of 7 days. 5 This is the ®rst report demonstrating that an MC4 receptor antagonist can increase food intake and body weight during chronic administration providing further evidence that the MC4 receptor is an important mediator of long term weight homeostasis.

Objectives: Here, we performed a pathophysiological examination of the vascular function of rodent in the presence of placental protein 13 (PP13) and its implication to regulate the development of preeclampsia. Methods: Single i.v. injection and prolonged in vivo exposure to PP13 via osmotic pumps were performed in gravid and non-gravid rats to examine the influence of PP13 on blood pressure and heart rate in animals. The effect of PP13 was also examined in isolated uterine and mesenteric arteries, along with the examination of placental blood supply. Results: Human PP13 has a major impact on the maternal cardiovascular system of rodents by reducing blood pressure, either at single or prolonged exposure, and causing significant vasodilatation in isolated arteries. Prolonged exposure was followed by increased elaboration and angiogenesis of the uteroplacental arteries supplying the placenta. Conclusion: This is the first study describing effects of PP13 on vasodilatation and uterine artery remodeling. The results imply that PP13 may have a physiological role in improving uteroplacental blood flow. The findings of this study make it tempting to speculate that keeping PP13 levels within a certain ‘therapeutic window' during pregnancy may facilitate proper adaptation of the maternal vasculature to pregnancy.

The central melanocortin system is involved in the regulation of food intake and body weight. In this study, we investigated the effect of a 4-week intracerebroventricular infusion of the melanocortin receptor agonist MT-II and the selective melanocortin-4 receptor antagonist HS024 on food intake and body weight homeostasis. The MT-IItreated rats ate less and lost considerably more weight than the control rats during the first week of treatment. During the second and third week, they gained weight and, by the end of the treatment period, the weight gain was similar to that of the control rats. The HS024 treatment caused hyperphagia and development of obesity during the entire period. Extensive accumulations of fat and a sixfold increase in leptin levels were observed in the HS024-treated rats, as compared with controls, after the 4-week period. Food conversion ratio, defined as body weight increase relative to weight of ingested food, was clearly increased in the HS024-treated rats, while it was lowered in the MT-II-treated rats compared with controls. The effect on food conversion ratio was transient, being greatest for both experimental groups during the first week and it was then attenuated to reach the level of controls at the end of the study. The results suggest that long-term injection of exogenous melanocortin receptor active substances may have an important transient effect on food conversion.