1 Relaxin (RLX) is a multifunctional hormone which, besides its role in pregnancy and parturition, has also been shown to influence the cardiovascular system. In this study, we investigated the effect of RLX on coronary flow of rat and guinea-pig hearts, isolated and perfused in a Langendorff apparatus. RLX was either added to the perfusion fluid at a concentration of 5 x 109 M for a 20-min perfusion, or given as a bolus into the aortic cannula at concentrations of 10-9 M, 5 x io-9 M and 10-8 M dissolved in 1 ml of perfusion fluid. 2 RLX, given either for a 20-min perfusion or as a bolus in the aortic cannula to guinea-pig and rat isolated hearts, increased the coronary flow and the amount of nitrite, a stable end-product of nitric oxide (NO) metabolism, that appeared in the perfusates in a concentration-dependent fashion. 3 The increase in coronary flow and in nitrite in the perfusates induced by RLX was significantly reduced by pretreatment with the nitric oxide synthase (NOS) 4 The effects of RLX on coronary flow and nitrite amounts in the perfusates were compared with those induced by the endothelium-dependent vasodilator agent, acetylcholine (ACh, I0--I0-M), and by the endothelium-independent vasodilator agent, sodium nitroprusside (SNP, I0--10-6 M). The results obtained show that RLX is more effective than ACh and SNP in increasing coronary flow. 5 The results of this study show that RLX increases coronary flow through stimulation of NO production; hence this hormone should be regarded as a novel agent capable of improving myocardial perfusion.

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The results of the current study demonstrate that relaxin inhibits histamine release by mast cells. This effect is related to the peptide concentrations, and could be observed in both isolated rat serosal mast cells stimulated with compound 48/ 80 or calcium ionophore A 23187, and in serosal mast cells isolated from sensitized guinea pigs and challenged with the antigen. The morphological findings agree with the functional data, revealing that relaxin attenuates calcium ionophore-induced granule exocytosis by isolated rat serosal mast cells. Similar effects of relaxin have also been recognized in vivo by light microscopic and densitometric analysis of the mesenteric mast cells of rats which received the hormone intraperitoneally 20 min before local treatment of the mesentery with calcium ionophore. Moreover, evidence is provided that relaxin stimulates endogenous production of nitric oxide and attenuates the rise of intracellular Ca2" concentration induced by calcium ionophore. The experiments with drugs capable of influencing nitric oxide production also provide indirect evidence that the inhibiting effect of relaxin on mast cell histamine release is related to an increased generation of nitric oxide. It is suggested that relaxin may have a physiological role in modulating mast cell function through the L-arginine-nitric oxide pathway. (J.

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SUMMARY1. Two preparations, a segment of rat ileum and the vagally innerved guinea-pig auricles, have been used in an analysis of the responses to vagal or to electrical field stimulation.2. The responses to parasympathetic stimulation were depressed by atropine and by tetrodotoxin, and potentiated by eserine.3. Supramaximal stimulation (10-20 Hz) resulted in increased release of acetylcholine and histamine, both in rat ileum and guinea-pig auricles.4. The release of histamine after parasympathetic stimulation did not exhibit tachyphylaxis, and it was not reproduced by non-parasympathetic stimuli.5. In both preparations, atropine produced a significant, dose-related reduction of histamine measured in the bath fluid after stimulation, while eserine increased histamine output.6. A significant diminution of mast cell granules metachromasia was observed in guinea-pig auricles and in rat intestine after parasympathetic stimulation.7. The possibility is discussed that acetylcholine released by parasympathetic stimulation would in turn evoke the secretion of histamine from tissue mast cells.

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White adipocyte differentiation was studied ultrastructurally in the mouse mammary gland following stimulation with 17β-estradiol and relaxin. These hormones have been previously demonstrated by us to induce hyperplasia and hypertrophy in the adipose cells of the mouse mammary gland. Following hormone treatment new fat cells are formed around the growing ducts. In these sites there is a close relationship between blood vessel growth and adipocyte development, and stromal areas featuring embryonic fat organs can frequently be found. In the sites of adipocyte differentiation the most numerous cell types are undifferentiated mesenchymal cells and preadipocytes, while fibroblasts and macrophages are much less common. No endothelial cells or pericytes were found detaching from the blood capillary walls. There were no fibroblasts or macrophages containing intracellular lipid deposits. Actively degranulating mast cells were frequent. The above findings strongly suggest the direct origin of adipocytes from perivascular mesenchymal cells, without the intermediate stages of well-differentiated fibroblasts, macrophages, endothelial cells or pericytes. The earliest morphologically recognizable stage in adipocyte differentiation is a ‘pale preadipocyte’, characterized by its irregular shape due to cytoplasmic processes, clear cytoplasmic matrix, well-developed organelles (especially ribosomes and Golgi apparatus), few and small lipid droplets, numerous pinocytotic vesicles and a very thin basal lamina. The next stage in adipocyte differentiation is a ‘dark pfreadipocyte’ showing a denser cytoplasmic matrix, reduced organelles and more abundant lipid accumulations. The pinocytotic vesicles are very numerous and the enveloping basal lamina is still thin. The subsequent maturation stages are the well-known globular multivacuolated adipocyte and finally the mature univacuolated, signet-ring, white adipocyte.

P-glycoprotein, an integral membrane protein acting as an energy-dependent efflux pump, has been detected immunocytochemically in the human pancreatic islets using C 494 monoclonal antibody. Intense P-glycoprotein immunoreactivity was found in both endothelial cells of islet blood capillaries and in endocrine cells. Strong expression of P-glycoprotein has been found in the capillary blood vessels at blood-tissue barrier sites and in numerous kinds of cells with secretory/excretory function. Therefore the present findings suggest that P-glycoprotein may play a role in controlling the composition of the extracellular fluids and the intracellular milieu of endocrine islet cells and possibly in regulating their secretory activity.