title: NaCl-induced hypertensive rat model of non-insulin-dependent diabetes: role of sympathetic modulation.
abstract: Systemic hypertension is common in individuals with non-insulin-dependent diabetes (NIDD) and, in this population, markedly increases the risk for cardiovascular complications. The aims of this study were to develop a rat model of combined NaCl-induced hypertension and NIDD, and to determine the contribution of the sympathetic nervous system to the development of the manifest hypertension. Two-day old male Wistar-Kyoto rats were injected with either streptozotocin (90 mg/kg, ip; NIDD) or vehicle (citrate buffer; control). At 4 weeks of age, the animals underwent either a right nephrectomy or a sham operation. Animals in each group were further subdivided, with one group maintained on normal (0.72 %) NaCl diet whereas the other was placed on a high (8%)-NaCl diet. At 6 months of age, diabetes was confirmed by glucose tolerance testing. Hemodynamic parameters were measured in the freely moving animal (ia) before and after the administration of prazosin (peripheral alpha1-adrenergic antagonist, iv) or clonidine (central alpha2-adrenergic agonist). The NIDD rat displayed a higher (P < .05) blood glucose concentration than the nondiabetic control rat during the glucose tolerance test. Elevated dietary NaCl significantly increased mean arterial pressure (MAP) in the uninephrectomized, but not the sham-operated groups. Acute administration of prazosin resulted in a significantly greater reduction in MAP of both hypertensive groups than of their normotensive counterparts. Moreover, clonidine caused a significant reduction in MAP of the hypertensive control rat but not in the normotensive controls. By contrast, both the hypertensive NIDD and the normotensive NIDD rats showed a similar reduction in MAP in response to clonidine administration. The data suggest that the combination of uninephrectomy and dietary NaCl excess confers hypertension on the NIDD rat. Moreover, enhancement of the sympathetic pathway plays an important role in the regulation of arterial pressure in the hypertensive NIDD rat.
authors.affiliation: Department of Oral Biology & Maxillofacial Pathology, Medical College of Georgia School of Dentistry, Augusta, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Mozaffari
authors.forename: C
authors.initials: C
authors.lastname: Patel
authors.forename: B K
authors.initials: BK
authors.lastname: Warren
authors.forename: S W
authors.initials: SW
authors.lastname: Schaffer
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists; D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003000:Clonidine / Q000008:administration & dosage; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D007275:Injections, Intravenous; D008297:Male; D011224:Prazosin / Q000008:administration & dosage; D051381:Rats; D011921:Rats, Inbred WKY; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D012982:Sodium, Dietary / Q000633:toxicity*; D013311:Streptozocin / Q000633:toxicity; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D012982:Sodium, Dietary; D013311:Streptozocin; D003000:Clonidine; D011224:Prazosin