ABSTRACT
BACKGROUND AND PURPOSE: We have reported that exposure to a diabetic intrauterine environment during pregnancy increases blood pressure in adult offspring, but the mechanisms involved are not completely understood. This study was designed to analyse a possible role of perivascular sympathetic and nitrergic innervation in the superior mesenteric artery (SMA) in this effect. EXPERIMENTAL APPROACH: Diabetes was induced in pregnant Wistar rats by a single injection of streptozotocin. Endothelium-denuded vascular rings from the offspring of control (O-CR) and diabetic rats (O-DR) were used. Vasomotor responses to electrical field stimulation (EFS), NA and the NO donor DEA-NO were studied. The expressions of neuronal NOS (nNOS) and phospho-nNOS (P-nNOS) and release of NA, ATP and NO were determined. Sympathetic and nitrergic nerve densities were analysed by immunofluorescence. KEY RESULTS: Blood pressure was higher in O-DR animals. EFS-induced vasoconstriction was greater in O-DR animals. This response was decreased by phentolamine more in O-DR animals than their controls. L-NAME increased EFS-induced vasoconstriction more strongly in O-DR than in O-CR segments. Vasomotor responses to NA or DEA-NO were not modified. NA, ATP and NO release was increased in segments from O-DR. nNOS expression was not modified, whereas P-nNOS expression was increased in O-DR. Sympathetic and nitrergic nerve densities were similar in both experimental groups. CONCLUSIONS AND IMPLICATIONS: The activity of sympathetic and nitrergic innervation is increased in SMA from O-DR animals. The net effect is an increase in EFS-induced contractions in these animals. These effects may contribute to the increased blood pressure observed in the offspring of diabetic rats.
Subject(s)
Diabetes Mellitus, Experimental/physiopathology , Mesenteric Arteries/innervation , Acetylcholine/pharmacology , Adenosine Triphosphate/metabolism , Animals , Blood Glucose/analysis , Blood Pressure , Body Weight , Diabetes Mellitus, Experimental/metabolism , Electric Stimulation , Female , Male , Mesenteric Arteries/metabolism , Mesenteric Arteries/physiopathology , Nitric Oxide/metabolism , Nitric Oxide Synthase Type I/metabolism , Pregnancy , Rats, Wistar , Sodium/metabolism , Superoxides/metabolism , Vasoconstriction , VasodilationABSTRACT
BACKGROUND AND PURPOSE: The present study was designed to determine how diabetes in pregnancy affects vascular function in their offspring, the influence of age and whether COX activation is involved in this effect. EXPERIMENTAL APPROACH: Relaxation responses to ACh were analysed in mesenteric resistance arteries from the offspring of control rats (O-CR) and those of diabetic rats (O-DR) at 3, 6 and 12 months of age. TxB2, PGE2 and PGF(2α) release were determined by enzyme immunoassay. COX-1 and COX-2 expression were measured by Western blot analysis. KEY RESULTS: O-DR developed hypertension from 6 months of age compared with O-CR. In O-DR, relaxation responses to ACh were impaired in all ages studied and were restored by COX-2 inhibition. TP receptor blockade (SQ29548) restored ACh relaxation in arteries from 3-month-old O-DR while TP and EP receptor blockade (SQ29548 + AH6809) was required to restore it in 6-month-old O-DR. In 12-month-old O-DR, ACh relaxation was restored when TP, EP and FP receptors were blocked (SQ29548 + AH6809 + AL8810). ACh-stimulated TxB2 was higher in all O-DR. ACh-stimulated PGE2 release was increased in arteries from 6- and 12-month-old O-DR, whereas PGF(2α) was increased only in 12-month-old O-DR. COX-2, but not COX-1, expression was higher in O-DR than O-CR. CONCLUSIONS AND IMPLICATIONS: The results indicate an age-dependent up-regulation of COX-2 coupled to an enhanced formation of vasoconstrictor prostanoids in resistance arteries from O-DR. This effect plays a key role in the pathogenesis of endothelial dysfunction, which in turn could contribute to the progression of vascular dysfunction in these rats.
Subject(s)
Cyclooxygenase 2/physiology , Diabetes Mellitus, Experimental/physiopathology , Endothelium, Vascular/physiopathology , Mesenteric Arteries/physiology , Prostaglandins/physiology , Acetylcholine/pharmacology , Age Factors , Animals , Blood Glucose/analysis , Blood Pressure , Cyclooxygenase 1/physiology , Female , Male , Membrane Proteins/antagonists & inhibitors , Membrane Proteins/physiology , Nitroprusside/pharmacology , Pregnancy , Rats , Rats, WistarABSTRACT
The aims of this study were to test a locally applied carvacrol gel and determine its efficacy preventing alveolar bone loss in experimental periodontitis in rats by regular methodology to validate applicability the atomic force microscopy (AFM) as a novel morphology method on this model. Wistar rats were subjected to ligature around second, upper-left molars. Animals were treated carvacrol gel topically (CAG), immediately after Experimental Periodontitis Disease induction for 1' three-times/day for 11 days. A vehicle gel was utilized as control. The periodontium and the surrounding gingivae were examined at regular histopathology and by AFM method; the neutrophil influx into the gingivae was also assayed using myeloperoxidase activity. The bacterial flora was assessed through culture of the gingival tissue. Alveolar bone loss was significantly inhibited by CAG group compared to the Vehicle (V) group, the carvacrol gel treatment reduced tissue lesion at histopathology, with preservation of the periodontium, coupled to decreased myeloperoxidase activity in gingival tissue and also prevented the proliferation of periodontal microorganisms and the weight loss. The GAC treatment preserved alveolar bone resorption and showed anti-inflammatory and antibacterial activities in experimental periodontitis. Topographical changes in histological sections were seen bringing into high relief the periodontal structures, being a simple and cost-effective method for periodontal evaluation with ultrastructural resolution.
