Impaired EDHF-mediated vasodilatation in adult offspring of rats exposed to a fat-rich diet in pregnancy

Abstract

We recently reported vascular dysfunction in adult offspring of rats fed a fat-rich (animal lard) diet in pregnancy. This study reports further characterization of constrictor and dilator function in mesenteric and caudal femoral arteries from 180-day-old offspring of dams fed the high fat diet (OHF). Endothelium-dependent relaxation in response to acetylcholine (10(-9)-10(-5)m) was impaired in mesenteric small arteries from male and female OHF compared with offspring of dams fed normal chow (males (maximum percentage relaxation): OHF 67.92 +/- 2.89, n= 8 versus control 92.08 +/- 2.19, n= 8, P < 0.01). Substantial relaxation in response to acetycholine in control mesenteric arteries remained after inhibition of nitric oxide synthase, soluble guanylate cyclase and cyclo-oxygenase but was blocked by 25 mm potassium. This component of relaxation, attributed to EDHF, was significantly reduced in OHF mesenteric arteries compared with controls. However, EDHF played a minor role in acetylcholine-induced relaxation in both control and OHF femoral caudal arteries (male and female). In these arteries, in contrast to mesenteric vessels, acetylcholine-induced relaxation was significantly enhanced in OHF but only in males (ACh (maximum percentage relaxation): OHF 58.40 +/- 4.39, n= 8 versus male controls 32.18 +/- 6.36, P < 0.05). This was attributable to enhanced nitric oxide-mediated relaxation. In conclusion, reduced endothelium-dependent relaxation in OHF mesenteric arteries is due to impaired EDHF-mediated relaxation. This defect was not apparent in femoral arteries in which EDHF has a less prominent role.

Figure 1. Endothelium-dependent relaxation to acetylcholine in third order mesenteric arteries of male and female offspring of dams fed a control diet during pregnancy and lactation

In PSS (○, n = 8), after incubation and in continued presence of indomethacin (▵, n = 5), after incubation and in continued presence of indomethacin, l-NAME and ODQ (▿, n = 5) and after incubation with indomethacin, l-NAME and ODQ and 25 mm K⁺ (□, n = 5). Data given as mean ± s.e.m.

Figure 2. Endothelium-dependent relaxation to acetylcholine in third order mesenteric arteries of male and female offspring of dams fed the fat-rich diet throughout pregnancy and lactation

In PSS (•, n = 8), after incubation and in continued presence of indomethacin (▴, n = 5), after incubation and in continued presence of indomethacin, l-NAME and ODQ (▾, n = 5) and after incubation with indomethacin, l-NAME, ODQ and 25 mm K⁺ (▪, n = 5). Data given as mean ± s.e.m.

Figure 3. Endothelium-dependent relaxation to acetylcholine in third order femoral arteries of male and female offspring of dams fed a control diet during pregnancy and lactation

In PSS (OC,○, n = 8), after incubation and in continued presence of indomethacin (▵, n = 5), after incubation and in continued presence of indomethacin, l-NAME and ODQ (▿, n = 5) and after incubation with indomethacin, l-NAME, ODQ and 25 mm K⁺ (□, n = 5). Data given as mean ± s.e.m.

Figure 4. Endothelium-dependent relaxation to acetylcholine in third order femoral arteries of male and female offspring of dams fed the fat-rich diet throughout pregnancy and lactation

In PSS (•, n = 8), after incubation and in continued presence of indomethacin (▴, n = 5), after incubation and in continued presence of indomethacin, l-NAME and ODQ (▾, n = 5) and, after incubation with indomethacin, l-NAME, ODQ and 25 mm K⁺ (▪, n = 5). Data given as mean ± s.e.m.

Figure 5. Responses to All in mesenteric (A) and femoral (B) resistance arteries of male and female offspring

Control dams (OC,○, n = 8) or offspring of fat-fed dams (OHF, •, n = 8). Data are expressed as mean (mN mm⁻¹) ± s.e.m. *P < 0.05 offspring of control dams versus offspring of fat-fed dams for maximal response.