The levels of several regulatory peptides were measured in peripheral plasma samples from individuals with chronic cardiac failure (CCF) and matched controls in both the resting state and during a short period of maximal exercise. Basal levels of noradrenaline (NA; 705 +/- 114 vs 195 +/- 54 ng.l-1; mean +/- SEM; P < 0.05), plasma renin activity (PRA; 12.9 +/- 2.9 vs 2.1 +/- 0.3 ng AI ml-1.h-1; P < 0.05) and aldosterone (ALDO; 325 +/- 49 vs 87 +/- 8 ng.l-1; P < 0.05) were all raised in the patients with CCF, and increased further with exercise. Basal circulating levels of atrial natriuretic peptide (ANP) were also significantly higher in the CCF group compared to controls (136 +/- 35 vs 27 +/- 5 ng.l-1; P < 0.01), but the response to exercise was attenuated, so that at peak exercise, no significant difference was observed. Basal circulating levels of gastrin-releasing peptide (GRP) (29 +/- 4 vs 40 +/- 4 ng.l-1; P < 0.05) and secretin (13 +/- 1 vs 32 +/- 4 ng.l-1; P < 0.05) were significantly lower in the CCF group when compared to controls and there was no significant change in the levels of either peptide with exercise. Levels of neurokinin A (NKA), neuropeptide Y (NPY) and neurotensin (NT) were somewhat higher in patients, but the differences were not significant, and there were no changes during exercise. There were also no significant differences in the levels of vasoactive intestinal peptide (VIP), glucose-dependent insulinotropic polypeptide (GIP), insulin or glucagon in either experimental group both before and during exercise. We have therefore identified different circulating levels of certain regulatory peptides in patients with CCF, but the significance of these remains unclear.

SummaryThe effect of simulated hyperglycaemia on bovine retinal pericytes was studied following culture of these cells for 10 days under normal (5 mmol/1) and elevated (25 mmol/1) glucose conditions in the absence of endothelial cells. Pericytes cultured under high ambient glucose exhibited both a delayed and reduced contractile response following stimulation with endothelin-1. Stimulation with 10 7 mol/1 endothelin-1 for 30 s caused significant contraction in cells grown in both 5 mmol/1 and 25 mmol/1 glucose. The former also contracted significantly with 10 -8 mol/1 endothelin-1. Further, at all concentrations tested, statistical comparison of the time course of contraction showed a significant difference (p < 0.02) in the reduction of planimetric surface area between the two cell groups. Since neither binding of endothelin-1 nor the number of receptors for this peptide were significantly different (p > 0.1) between bovine retinal pericytes grown for 10 days under normo-or hyperglycaemic conditions, it became apparent that the altered contractility in bovine retinal pericytes following culture in high glucose must be due to post-binding intracellular disturbance(s). Indeed, both basal and 15 s post-stimulation with 10-8 mol/1 endothelin-1, levels of inositol trisphosphate were significantly reduced (p < 0.05 andp < 0.02, respectively) in pericytes cultured for 10days in 25 mmol/1 glucose. These results show that endothelialindependent alterations in contractility of pericytes occur when they are grown in conditions which simulate hyperglycaemia. The results also suggest that the observed attenuation in response to endothelin-1 stimulation evident in pericytes grown under simulated hyperglycaemic conditions is not due to alterations in peptide binding. [Diabetologia (1994) 37: 36-42] Key words Retinal microvascular pericytes, hyperglycaemia, endothelin-1, inositol (1,4,5) trisphosphate.The retinal microcirculation is devoid of extrinsic innervation and there is evidence that under normal conditions retinal blood flow may be regulated by changes in smooth muscle and pericyte tone mediated by endothelium-derived autacoids acting in paracrine fashion [1]. Recent work has shown that retinal capillary endothelial cells secrete endothelin-1 (ET-1), a potent vasoconstrictor, and that corresponding pericytes bear receptors to this peptide, suggesting the presence of a . ET-1 was first characterized and sequenced from the supernatant of cultured porcine aortic endothelial cells by Yanagisawa et al. [3]. It is the most potent vasoconstrictor known, causing contraction of vascular strips from humans and experimental animals in vitro [4], and is highly effective at the microcirculatory level [5]. We have previously demonstrated that ET-1 induces rapid increases in intracellular inositol (1,4,5) trisphosphate [Ins(1,4,5)P3] levels in cultured retinal pericytes and causes a sustained contraction response in these cells [6]. ET-1 also acts as a co-mitogen in pericytes in the presence of low levels of fetal calf serum [6]. ...

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Levels of gastrin-releasing peptide (GRP) were determined by radioimmunoassay in human normal main and lobar bronchus and parenchymal lung tissue extracts. It was found that the level of GRP differed significantly between all 3 areas. The concentration of GRP was statistically higher in main bronchus (median 6.74 ng/g) compared to both lobar bronchus (median 4.79 ng/g) and parenchymal lung (median 1.73 ng/g), and also statistically higher in lobar bronchus compared to parenchymal lung. Chromatographically, GRP-immunoreactivity in both main and lobar bronchial extracts corresponded to GRP1-27 and GRP18-27, while in lung tissue only one major species was identified which corresponded in retention time to GRP18-27. No significant difference was detected when the levels of GRP in normal lobar bronchus and normal lung tissue were compared to the levels in lobar bronchus and lung taken from patients with lung carcinoma, at a site adjacent to the carcinoma. However, a significant difference was observed between the GRP content of normal main bronchus compared to main bronchus from patients with carcinoma. GRP was measured in 26/56 lung carcinomas examined. The levels ranged from 42,000 ng/g in a carcinoid tumour to 0.18 ng/g in a squamous-cell carcinoma, though only in 6 tumours were the levels outside the range determined for normal pulmonary tissue. Chromatography of selected tumour extracts of different histopathologies showed that there were differences in the GRP products present.