Radiotelemetric monitoring of blood pressure and mesenteric arterial bed responsiveness in rats with streptozotocin-induced diabetes

We investigated the changes in arterial blood pressure (BP) and of mesenter ic arterial bed (MAB) responsiveness that accompany streptozotocin (STZ)-in duced diabetes. BP was recorded by radiotelemetry in conscious animals befo re and during a 4-week period following induction of the diabetic state wit h STZ. At the end of this period, the MAB was isolated and perfused under c onstant flow conditions: perfusion pressure (PP, mmHg) was taken as an inde x of arteriolar tone. BP was lower (P < 0.05) in STZ-treated diabetic rats (82.9 +/- 5.0 mmHg) than in vehicle-treated rats (108.9 +/- 6.3 mmHg). Basa l perfusion pressure of the MAB was lower in STZ-treated rats than in contr ol rats and inhibition of nitric oxide (NO) synthesis with N-G-nitro-L-argi nine-methyl-ester and N-G-nitro-L-arginine (100 mu M each) failed to change this relationship. Increases in PP of MAB to phenylephrine (Phe), norepine phrine (NE), and potassium chloride (KCl) were reduced in STZ-treated rats compared with control rats. Inhibition of NO synthesis reduced responses to Phe, NE, and KCL in both STZ and control rats. The reduced responsiveness of STZ rats to Phe, NE, and KCl persisted after inhibition of NO synthesis. Acetylcholine (ACh) evoked relaxation of the MAB in a dose-dependent fashi on. Maximal responses to ACh, but not sodium nitroprusside, were lower in S TZ rats than in vehicle treated rats. Inhibition of NO synthesis reduced re sponses to ACh in both STZ and control rats. The reduced responsiveness of STZ rats to ACh persisted after inhibition of NO synthesis. The data demons trate that STZ-induced diabetes is associated with a fall in blood pressure when pressure is recorded with radiotelemetry. The fall in blood pressure may be related to a non-specific decrease in responsiveness to vasoconstric tor stimuli mediated at least in part by NO-independent mechanisms. A decre ase in responsiveness to endothelial dependent vasodilator mechanisms appea red insufficient to restore responsiveness to vasoconstrictor stimuli.