093P Brighton
Winter Meeting December 2007 |
Vasodilator responses to acetylcholine and sodium nitroprusside in conscious fructose-fed rats
Kirsten Smith, Julie March, Philip Kemp, Sheila Gardiner, Terence Bennett
University of Nottingham, Nottingham, United Kingdom
Chronic fructose feeding can cause hypertension in normotensive rats, and in vitro studies indicate that endothelial dysfunction precedes the hypertension (Katakam et al., 1998). The aim of this study was to assess endothelium-dependent (acetylcholine, ACh) and endothelium-independent (sodium nitroprusside, SNP) vasodilator responses in vivo, following fructose-feeding.
Male, Sprague-Dawley rats (300-400g) were given a control diet or a diet containing 60% fructose for 4 weeks. After 2 weeks of feeding, pulsed Doppler flow probes were implanted (renal (R), mesenteric (M) and hindquarters (H)), and about 10 days later, catheters were inserted in the jugular vein and caudal artery. All surgery was under general anaesthesia (fentanyl and medetomidine, 300μg kg-1 i.p.). At least 24hrs after catheter implantation, heart rate (HR), mean blood pressure (BP) and regional vascular conductances (VC) were measured and responses to 3 min i.v. infusions of ACh (10μg kg-1 min-1) and SNP (37.5μg kg-1 min-1) were recorded.
Resting HR (356 ± 8, 348 ± 15 beats min-1), BP (105 ± 3, 106 ± 3 mmHg), RVC (82 ± 12, 87 ± 11 (kHz mmHg-1)103), and MVC (65 ± 8, 62 ± 2 (kHz mmHg-1)103) were not different in control and fructose-fed rats, but HVC was lower (P<0.05, Mann-Whitney test) in fructose-fed rats than in controls (42 ± 5, 62 ± 7 kHz mmHg-1 103). In control rats, ACh caused vasodilatation mainly in the renal vascular bed, and SNP caused vasodilatation mainly in the mesenteric vascular bed. In fructose-fed rats, the renal vasodilator response to ACh and the mesenteric vasodilator effect of SNP were enhanced (Table 1).
Table 1. Integrated (0-3 min) responses (mean ± s.e.m.) to ACh and SNP in control (C; n=8) and fructose-fed (F; n=7) rats. Units are HR (beats), BP (mmHg min), VC ((kHz mmHg-1)103 min). *P<0.05 vs. corresponding control (Mann-Whitney test).
|
HR |
BP |
RVC |
MVC |
HVC |
| C ACh |
+197±28 |
-16±3 |
+106±13 |
-44±6 |
+14±4 |
| F ACh |
+196±18 |
-21±6 |
+141±13* |
-36±9 |
+18±1 |
| C SNP |
+327±23 |
-76±9 |
+77±14 |
+104±22 |
+32±8 |
| F SNP |
+285±39 |
-89±9 |
+90±18 |
+202±32* |
+47±12 |
These results are not consistent with in vitro data showing impaired endothelium-dependent vasodilatation in fructose-fed rats (Katakam et al., 1998). Since the renal vasodilator response to ACh in vivo is nitric oxide-dependant (Gardiner et al, 1991), the findings of enhanced renal responses to ACh and mesenteric responses to SNP are consistent with up-regulation of the soluble guanylyl cyclase/cGMP system in fructose-fed rats.
Gardiner S M et al. (1991) Br J Pharmacol 103: 1725-32
Katakam P V et al. (1998) Am J Physiol 275: R788-R792
Research supported by the MRC.
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