Effect of high fat loading in Dahl salt-sensitive rats

Abstract

Salt sensitivity of blood pressure (BP) is speculated to be a characteristic in obesity-induced hypertension. To elucidate the influence of obesity on salt-sensitive hypertension, we examined the effect of fat loading on BP, renal damage, and their progression induced by salt excess in Dahl salt-sensitive (S) rats. High fat (HF: 45% fat diet: 8 weeks) diet increased BP with greater weight gain and visceral fat accumulation than low fat (10% fat) diet. In HF-fed rats, plasma glucose, plasma insulin, and urinary catecholamine increased, and urinary protein tended to be elevated. Moreover, excessive salt (8% salt diet: 8 weeks)-induced hypertension and proteinuria was accelerated in HF-fed rats. Therefore, fat loading increased BP in Dahl S rats possibly through insulin-resistance and sympathetic excitation. Moreover, fat loading accelerated salt-induced BP elevation and renal damage, suggesting excessive intake of both fat and salt, such as a civilized diet, exert the synergic harmful effects.

Figure 1

Changes in body weight and visceral fat accumulation with fat loading. (A) After 6 weeks of the treatment, body weight was increased in both groups of rats but its extent was greater in high fat (HF)-fed rats (n = 12) compared to low fat (LF)-fed rats (n = 10). (B) Visceral (retroperitoneal, epididymal, and mesenteric) fat weights were higher in HF-fed rats. *P < 0.05, ^†P < 0.01 vs. LF-fed rats, respectively.

Figure 2

Changes in systolic blood pressure (SBP) with fat loading. SBP was significantly increased in high fat (HF)-fed rats (n = 12) compared with low fat (LF)-fed rats (n = 10) after 2 weeks of treatment. *P < 0.01 vs. LF-fed rats, respectively.

Figure 3

Urinary norepinephrine excretion in high fat (HF)- and low fat (LF)-fed rats (n = 5, respectively). Urinary norepinephrine was significantly increased at 2 and 4 weeks of the treatment in HF-fed rats. Similarly, urinary epinephrine was increased at 4 weeks of the treatment in HF-fed rats. *P < 0.05, ^†P < 0.01 vs. LF-fed rats, respectively.

Figure 4

Changes in urinary protein with fat loading. Urinary protein has tendency to be increased at the late phase (6 and 8 weeks) of fat loading in high fat (HF)-fed but not in low fat (LF)-fed rats (n = 5, respectively).

Figure 5

Salt-induced rise in systolic blood pressure (SBP) and urinary protein in high fat (HF)-fed rats (n = 6) and low fat (LF)-fed rats (n = 5). (A) SBP was greater after salt loading in HF-fed rats after 8 weeks of treatment. (B) Urinary protein was also increased in HF-fed rats. *P < 0.05, ^†P < 0.01 vs. LF-fed rats, respectively.

Figure 6

Representative micrographs of periodic acid-Schiff-stained renal (A) and glomerular (B) sections from high fat (HF)-fed rats and low fat (LF)-fed rats before and after salt loading. In salt-fed HF-fed rats, glomerular, tubulointerstitial, and arteriolar damages were more severe. The bar represents 100 μm. The histological findings were confirmed in two kidneys from each group at each point of time.