125I-labeled rat amylin binds to specific sites in the cortex of rat kidney, which can be distinguished from those for 125I-labeled salmon calcitonin (sCT) and 125I-labeled rat alpha-calcitonin gene-related peptide (alpha-CGRP) on the basis of regional distribution. These sites have a high affinity (approximately 1 nM) for amylin, and 125I-amylin binding is potently inhibited by the peptide antagonists AC413 and sCT-(8-32), whereas CGRP-(8-37) is a poor inhibitor of binding. Furthermore, incubation with guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) inhibits 125I-amylin binding by > 90%, indicating that binding is dependent on coupling to G proteins. In renal cortex, amylin stimulated adenylyl cyclase activity three- to fourfold, and this was inhibited by AC413 and sCT-(8-32) but not by CGRP-(8-37). Amylin activated plasma renin twofold, and this was blunted by prior administration of AC413 but not CGRP-(8-37). We speculate that amylin may play an important role in renal physiology and that in states of hyperamylinemia, as found in obesity and the insulin resistance syndrome, this peptide may be involved in the genesis and development of hypertension.

In experimental diabetes, the mesenteric vascular tree undergoes hypertrophy, and this is associated with an increase in mesenteric angiotensin-converting enzyme (ACE) levels. The aim of this study was to determine if inhibition of mesenteric ACE by ACE inhibition would influence diabetes-associated mesenteric vascular hypertrophy. Control or streptozocin-induced diabetic rats were randomized to receive no drug or the ACE inhibitor perindopril. In addition, other diabetic rats were randomized to receive either low-dose insulin that does not alter glycemic control or high-dose insulin, administered as a silastic pellet to achieve euglycemia. After 3 weeks, animals were killed for measurement of mesenteric ACE, vessel weight, and wall:lumen ratio. Diabetes was associated with increased mesenteric ACE levels, increased vessel weight, and an increase in the wall:lumen ratio. ACE inhibition, despite no effect on glycemic control, food intake, urinary urea excretion, or gut weight, prevented the increase in mesenteric ACE levels and attenuated mesenteric vascular hypertrophy as assessed by weight or wall:lumen ratio. The increase in staining by an antibody to the endothelial product, von Willebrand factor, in diabetic rats was totally prevented by perindopril treatment. Euglycemia but not low-dose insulin therapy in the diabetic rats normalized mesenteric vessel ACE, weight, and wall:lumen ratio. In conclusion, ACE inhibition may have a specific role in preventing diabetes-associated vascular hypertrophy, an important process in the genesis of micro- and macrovascular diabetic complications.

No abstract

No abstract