title: Chronic salt loading and cardiovascular-associated changes in experimental diabetes in rats.
abstract: 1. High-sodium intake may increase blood pressure and diabetes is a salt-sensitive condition. In the present study, we evaluated cardiovascular changes and their neurohumoral mechanisms in streptozotocin (STZ)-diabetic rats that underwent chronic salt loading. 2. We studied male Wistar rats (150-280 g) 14 days after the injection of either STZ (50 mg/kg, i.v.; D; n = 18) or citrate buffer (C; n = 16). After the induction of diabetes, animals were maintained for 14 days with free access to standard rat chow and tap water (C and D groups) or 1% NaCl solution (C-S and D-S groups). We conducted two experiments. Experiment 1 consisted of basal arterial pressure (AP) measurement (30 min) followed by the evaluation of AP responsiveness to phenylephrine and sodium nitroprusside. One day later, with the rats anaesthetized, a blood sample was collected to test for glycaemia, plasma angiotensin-converting enzyme (ACE) activity and renin. Kidneys were removed for the determination of tissue ACE activity. Experiment 2 comprised 24 h urine collection followed by 3 days of cardiovascular records, which consisted of a 30 min basal AP measurement, followed by injection of blockers of the vasopressin system, the renin-angiotensin system (RAS) and the sympathetic system. Basal haemodynamic data, baroreflex evaluation and AP responses to blockade of the vasopressin system with vasopressin V(1) receptor antagonist (aAVP; 10 mg/kg, i.v.), the RAS by losartan (10 mg/kg, i.v.) and the sympathetic system by hexamethonium (20 mg/kg, i.v.) were determined. 3. Glycaemia was similar between C and C-S (P = 0.612) and between D and D-S (P = 0.552), but higher in diabetic compared with non-diabetic rats (P < 0.0001). The D-S rats had an increment of 24% in mean AP compared with D (120 +/- 4 vs 97 +/- 2 mmHg, respectively; P = 0.0001), which was not seen in C-S compared with C rats. A positive association was noted between urinary sodium and mean AP (r = 0.37; P = 0.04). Plasma renin was undetectable in D-S rats. The response to acute drug blockade of vasopressin and the RAS was similar among groups, but hexamethonium elicited a more pronounced decrease in AP in D-S compared with D rats (P = 0.001). 4. The main neurohumoral mechanisms of salt-induced cardiovascular changes in STZ-diabetes are increased sodium and vascular sensitivity to adrenergic stimuli, which act in combination to produce a final result of higher AP levels, a finding not observed in control rats. Baroreflex derangements induced by diabetes were not affected by salt overload.
authors.affiliation: Hypertension Unit, Heart Institute, University of São Paulo, São Paulo, and Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: C  Y
authors.initials: C
authors.lastname: Maeda
authors.forename: B  D
authors.initials: B
authors.lastname: Schaan
authors.forename: E  M
authors.initials: E
authors.lastname: Oliveira
authors.forename: V  L
authors.initials: V
authors.lastname: Oliveira
authors.forename: K
authors.initials: K
authors.lastname: De Angelis
authors.forename: M  C
authors.initials: M
authors.lastname: Irigoyen
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology; D017704:Baroreflex / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000378:metabolism / Q000503:physiopathology* / Q000652:urine; D005730:Ganglionic Blockers / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006400:Hematocrit; D018738:Hexamethonium / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D006973:Hypertension / Q000097:blood / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology* / Q000652:urine; D007668:Kidney / Q000201:enzymology / Q000473:pathology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D009929:Organ Size; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects; D017673:Sodium Chloride, Dietary; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D014667:Vasopressins / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001786:Blood Glucose; D005730:Ganglionic Blockers; D006727:Hormone Antagonists; D017673:Sodium Chloride, Dietary; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D014667:Vasopressins; D001127:Arginine Vasopressin; D009599:Nitroprusside; D010656:Phenylephrine; D018738:Hexamethonium; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D019808:Losartan