Neovascularization in the retina and iris of diabetic patients is a major cause of severe visual loss. However, study of these lesions is compromised by the lack of a comparable diabetic rodent model. Because the vasoactive and angiogenic agent, angiotensin II, is involved in diabetic microvascular disease, we aimed to determine whether endothelial cell proliferation could be induced in the retinae and irides of hypertensive transgenic (mRen-2)27 rats that display an enhanced extra-renal renin-angiotensin system (RAS), including the eye. Six-week-old Ren-2, spontaneously hypertensive, and Sprague-Dawley rats received either streptozotocin or control vehicle and were studied for 36 weeks. Additional nondiabetic and diabetic Ren-2 rats were treated throughout with the angiotensin-converting enzyme inhibitor lisinopril (LIS) (10 mg/kg/day in drinking water). Endothelial cell proliferation was only observed in retinae and irides of diabetic Ren-2 rats and was reduced with LIS. In diabetic Ren-2, vascular endothelial growth factor (VEGF) and VEGFR-2 mRNA were increased in retinae and irides and reduced with LIS. Diabetes activated ocular renin in Ren-2 but not Sprague-Dawley rats. The diabetic Ren-2 rat is a model of intraocular endothelial cell proliferation that can be attenuated by RAS blockade via VEGF-dependent pathways. RAS blockade is a potential treatment for vision-threatening diabetic microvascular complications.

1 Vascular responses to local injection of dopamine and isoprenaline have been compared in the blood-perfused gracilis muscle and hind paw pads of dogs anaesthetized with chloralose.2 In the paw pads, dopamine (0.5 to 5.0 gg) caused a transient vasoconstriction followed by dosedependent vasodilatation. a-Adrenoceptor blockade converted this response to pure vasodilatation, which was attenuated or abolished by the dopamine-receptor antagonist, haloperidol (1 to 2mg i.a.). In the gracilis, dopamine produced only vasoconstriction. Following a-adrenoceptor blockade this was abolished, but only a very small dilator response was revealed. 3 Isoprenaline (0.05 to 0.5 jig) caused dose-dependent dilatation in both beds, which was attenuated by propranolol (0.1 mg/kg i.v.).4 Glyceryl trinitrate (0.2 to 5.0 gg) was used to assess vascular reactivity. When responses to isoprenaline and dopamine were compared with those to glvceryl trinitrate, both beds had approximately equal reactivity to isoprenaline. In contrast the paw pads were 10 fold more responsive to dopamine than was the gracilis. 5 We conclude that the vessels of the paw pads play an important part in the femoral dilator response to dopamine.

Secretion of prorenin from extrarenal tissues comprises approximately half of the renin protein in plasma; its origin is unknown.

Limy bile, characterized by excessive precipitation of calcium carbonate, is an uncommon complication or gallstone disease, and is a condition that seems to follow gall‐bladder obstruction. Limy bile was observed at cholecyslectomy irra 57 year old woman who presented with biliary colic. At operation a mass of precipitated cohesive crystals, that had coalesced into a whitish paste of calcium carbonate, was observed obstructing the outlet of the gall‐bladder. This case report is unique in that calcium carbonate precipitation appears to have preceded gall‐bladder obstruction.