Short-term streptozotocin-induced diabetes induces blood pressure decrease associated with reduced aortic 45Ca2+ uptake and selective depression of the sustained noradrenergic contraction

To test the hypothesis that diabetes can selectively affect the intracellular and extracellular components of the noradrenergic vascular response in rats, we studied changes in blood pressure, in vitro vascular contraction a nd Ca-45(2+) uptake in experimental diabetes induced by injection of 60 mg/kg of streptozotocin (STZ). One week after induction of diabetes mean blood pressure decreased significantly from 106 +/- 3 mmHg to 89 +/- 2 mmHg. After incubation in Ca2+ = 1.6 mM, contraction of STZ aortic rings to 10(-7) M of norepinephrine was preserved in its intracellular component (Control: 231 +/- 28, STZ: 274 +/- 22 mgForce/mgTissue, NS) but depressed in its extracellular component (Control: 277 +/- 24, STZ: 133 +/- 33 mgForce/mgTissue, P < 0.05). Uptake of Ca-45(2+) in the same rings was depressed in both components. Norepinephrine contractions due to extracellular Ca2+ (prior depletion of norepinephrine-sensitive Ca2+ stores) unexpectedly exhibited a initial component whose magnitude in control rings was similar to the response due to intracellular Ca2+ (extra: 503 +/- 65 mg, intra: 411 +/- 30 mgForce/mgTissue), and was not depressed in STZ preparations (399 +/- 62 mgForce/mgTissue). The sustained contraction to norepinephrine in extracellular Ca2+ was significantly reduced in STZ aortas (1163 +/- 92 vs. 528 +/- 95 mgForce/mgTissue). We conclude that: 1) Short-term streptozotocin-induced diabetes features reduced blood pressure along with deficient aortic Ca-45 uptake and contraction to norepinephrine, and 2) Only the sustained phase of the norepinephrine contraction, dependent on extracellular Ca2+, was depressed in the diabetic rats and could possibly be associated with the observed fall in blood pressure.