Increased myogenic responses of resistance-sized mesenteric arteries after reduced uterine perfusion pressure in pregnant rats.

OBJECTIVE: A central component of preeclampsia is a reduction in utero-placental perfusion. We tested the hypothesis that vascular reactivity of second - order mesenteric arteries would be increased in a pregnant rat with reduced uterine perfusion pressure (RUPP). METHODS: Pregnant 10-12 week old Sprague-Dawley rats underwent RUPP surgery on gestational day 14, and experiments were carried out on day 20. SHAM operated animals were used as controls. Resistance caliber mesenteric arteries (200-250 µm) were isolated, myogenic reactivity and responses to vasoconstrictor and vasodilator agonists were assessed utilizing a pressurized arteriograph system. RESULTS: RUPP resulted in maternal hypertension and reductions in fetal number and weight. Resistance caliber mesenteric arteries (200-250 µm) were isolated, myogenic reactivity and responses to vasoconstrictor and vasodilator agonists were assessed utilizing a pressurized arteriograph system. Myogenic reactivity responses were normalized as a percent change in vessel diameter from an initial diameter at 20 mmHg. The mesenteric arteries from RUPP animals exhibited a significant increase in myogenic reactivity compared to SHAM controls (p < 0.05). This increased myogenicity was reversed with prostaglandin inhibition, suggesting a role for a vasoconstrictor prostaglandin. In addition to alterations in myogenic reactivity, resistance-sized arteries from RUPP animals have decreased responses to nitric oxide (NO) as evidenced by decreases in responses to methacholine (ME; P < 0.05) and no change in myogenic reactivity after NO synthase blockade. CONCLUSION: RUPP alters the behavior of resistance caliber arteries to favor a more contractile phenotype with decreased in NO responses, which is similar to what is seen in preeclampsia.

Moderate ascorbate deficiency increases myogenic tone of arteries from pregnant but not virgin ascorbate-dependent rats.

Plasma ascorbic acid is decreased in women with the pregnancy disorder preeclampsia. We used a mutant strain of rats (Osteogenic Disorder Shionogi), dependent on dietary sources of vitamin C, to investigate whether reduced intake of the vitamin would differentially affect vascular function in late-pregnant (day 19) and age-matched virgin rats. The animals were given either 1 mg/mL of ascorbic acid ad libitum in drinking water [fully supplemented (FS)] or 0.25 mg/mL [marginally supplemented (MS)]. Fetal weights were 21% lower in MS than FS rats, whereas mean maternal weights and pup numbers did not differ. Small mesenteric arteries (diameter, 268+/-7 microm) were mounted in a pressurized arteriograph. Myogenic reactivity (contractile response to step increases in intraluminal pressure) was increased in arteries from MS pregnant compared with FS pregnant rats to levels observed in virgin rats. Ascorbic acid intake did not affect myogenic responses of arteries from virgin rats. Hence, the normal pregnancy-induced reduction in myogenic reactivity was abrogated in MS pregnant animals. Inhibition of nitric oxide synthase had no effect on the myogenicity of arteries from virgin or MS pregnant rats but increased myogenicity of FS pregnant rats to the level of MS pregnant rats. Free radical scavengers reversed the accentuated myogenicity of MS pregnant rats without affecting FS pregnant or virgin rat arteries. These data indicate that moderate ascorbate deprivation increases mesenteric artery myogenic responsiveness during pregnancy. This increase may result from a decrease in nitric oxide-mediated modulation of the myogenic contractile response.

Myogenic reactivity is reduced in small renal arteries isolated from relaxin-treated rats.

Administration of the ovarian hormone relaxin to nonpregnant rats vasodilates the renal circulation comparable to pregnancy. This vasodilation is mediated by endothelin (ET), the ET(B) receptor, and nitric oxide. Furthermore, endogenous relaxin mediates the renal vasodilation and hyperfiltration that occur during gestation. The goal of this study was to investigate whether myogenic reactivity of small renal and mesenteric arteries is reduced in relaxin-treated rats comparable to the pregnant condition. Relaxin or vehicle was administered to virgin female Long-Evans rats for 5 days at 4 microg/h, thereby producing midgestational blood levels of the hormone. The myogenic responses of small renal arteries (200-300 microm in diameter) isolated from these animals were evaluated in an isobaric arteriograph system. Myogenic reactivity was significantly reduced in the small renal arteries from relaxin-treated compared with vehicle-treated rats. The reduced myogenic responses were mediated by the ET(B) receptor and nitric oxide since the selective ET(B) receptor antagonist RES-701-1 and the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester restored myogenic reactivity to virgin levels. The influence of relaxin was not limited to the renal circulation because myogenic reactivity was also reduced in small mesenteric arteries isolated from relaxin-treated rats. Thus relaxin administration to nonpregnant rats mimics pregnancy, insofar as myogenic reactivity of small renal and mesenteric arteries is reduced in both conditions.