Short-term streptozotocin-induced diabetes induces blood pressure decrease associated with reduced aortic (45)Ca(2+) 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 and (45) Ca(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 Ca(2+) =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 (45) Ca(2+) in the same rings was depressed in both components. Norepinephrine contractions due to extracellular Ca(2+) (prior depletion of norepinephrine-sensitive Ca(2+) stores) unexpectedly exhibited a initial component whose magnitude in control rings was similar to the response due to intracellular Ca(2+) (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 Ca(2+) 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 (45) Ca uptake and contraction to norepinephrine, and 2) Only the sustained phase of the norepinephrine contraction, dependent on extracellular Ca(2+), was depressed in the diabetic rats and could possibly be associated with the observed fall in blood pressure.
Rebolledo
A
A
National Council for Scientific and Technical Research (CONICET), Faculdad de Ciencias Exactas, Departmento de Ciencias Biológicas, Universidad Nacional de La Plata, Argentina.
Ayala-Paredes
F
F
Milesi
V
V
Grassi
A O
AO
Rinaldi
G J
GJ
D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology / Q000503:physiopathology*; D001794:Blood Pressure / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes / Q000493:pharmacokinetics; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000503:physiopathology*; D007022:Hypotension / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000502:physiology / Q000503:physiopathology*; D009638:Norepinephrine / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013997:Time Factors
D002132:Calcium Radioisotopes; D011189:Potassium Chloride; D002118:Calcium; D009638:Norepinephrine