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

Clin Exp Pharmacol Physiol. 2007 Jul;34(7):574-80. doi: 10.1111/j.1440-1681.2007.04625.x.

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.

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / pharmacology
  • Animals
  • Arginine Vasopressin / analogs & derivatives
  • Arginine Vasopressin / pharmacology
  • Baroreflex* / drug effects
  • Blood Glucose / metabolism
  • Blood Pressure* / drug effects
  • Body Weight
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / physiopathology*
  • Diabetes Mellitus, Experimental / urine
  • Ganglionic Blockers / pharmacology
  • Heart Rate* / drug effects
  • Hematocrit
  • Hexamethonium / pharmacology
  • Hormone Antagonists / pharmacology
  • Hypertension / blood
  • Hypertension / chemically induced
  • Hypertension / metabolism
  • Hypertension / physiopathology*
  • Hypertension / urine
  • Kidney / enzymology
  • Kidney / pathology
  • Losartan / pharmacology
  • Male
  • Nitroprusside / pharmacology
  • Organ Size
  • Peptidyl-Dipeptidase A / blood
  • Peptidyl-Dipeptidase A / metabolism
  • Phenylephrine / pharmacology
  • Rats
  • Rats, Wistar
  • Renin / blood
  • Renin-Angiotensin System* / drug effects
  • Sodium Chloride, Dietary
  • Sympathetic Nervous System / drug effects
  • Sympathetic Nervous System / metabolism
  • Sympathetic Nervous System / physiopathology*
  • Vasoconstrictor Agents / pharmacology
  • Vasodilator Agents / pharmacology
  • Vasopressins / antagonists & inhibitors
  • Vasopressins / metabolism*

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Blood Glucose
  • Ganglionic Blockers
  • Hormone Antagonists
  • Sodium Chloride, Dietary
  • Vasoconstrictor Agents
  • Vasodilator Agents
  • Vasopressins
  • Arginine Vasopressin
  • Nitroprusside
  • Phenylephrine
  • Hexamethonium
  • vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-
  • Peptidyl-Dipeptidase A
  • Renin
  • Losartan