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Clinical and experimental pharmacology & physiology

Chronic salt loading and cardiovascular-associated changes in experimental diabetes in rats.


PMID 17581211

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.

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V2255
[β-Mercapto-β,β-cyclopentamethylenepropionyl1, O-me-Tyr2, Arg8]-Vasopressin, ≥97% (HPLC)
C52H74N14O12S2