Effects of pregnancy, hypertension and nitric oxide inhibition on rat uterine artery myogenic reactivity

Abstract

Background/aims: The purpose of this study was to examine the effects of hypertension and nitric oxide (NO) inhibition on myogenic tone in uterine arteries during pregnancy.

Methods: Premyometrial radial uterine arteries from nonpregnant and late pregnant Sprague-Dawley rats were evaluated for myogenic reactivity from the following groups: control, hypertensive/NO-inhibited (L-NAME treatment) and normotensive/NO-inhibited (L-NAME plus hydralazine).

Results: In both nonpregnant and pregnant animals, L-NAME treatment significantly elevated blood pressures, while the addition of hydralazine made the animals normotensive. In nonpregnant animals, little myogenic tone was seen in controls; tone increased significantly in the L-NAME group, and was attenuated in those treated with L-NAME plus hydralazine. In pregnant animals, controls developed significant tone; this was reduced in the L-NAME group, and returned to control levels in the L-NAME plus hydralazine group.

Conclusions: Dimensional measurements showed that arteries from the pregnant hypertensive group did not undergo expansive remodeling, suggesting that tone development is related to phenotypic alterations in vascular smooth muscle and/or altered physical forces secondary to adaptive changes in arterial diameter. These differences implicate pregnancy-specific pathways in the development and inhibition of myogenic tone, and point to potentially opposing roles of NO and hypertension.

Fig. 1

Representative experimental tracing showing the relationship between transmural pressure and lumen diameter in a uterine radial artery from an LP-L+H animal. Note the development of tone during equilibration at 60 mm Hg, and additional constriction following the addition of 0.2 mM L-NNA + 10 μM indomethacin to inhibit endogenous NO and prostanoid production, respectively. Once tone developed, lowering pressure to 20 mm Hg induced an inhibition of constriction, with passive responses in diameter to elevations in pressure to 40 mm Hg. Tone redeveloped at 60 mm Hg, and was maintained up to 140 mm Hg, at which point forced dilatation occurred.

Fig. 2

a Myogenic tone (%) in uterine radial vessels from all treatment groups at 80 mm Hg. The levels of tone in vessels from nonpregnant L-NAME (NP-L, n = 7), late pregnant control (LP-C, n = 6), and late pregnant L-NAME + hydralazine (LP-L+H, n = 8) groups were statistically similar to each other, and different from nonpregnant control (NP-C, n = 4), nonpregnant L-NAME + hydralazine (NP-L+H, n = 6), and late pregnant L-NAME (LP-L, n = 8) animals (all of which were statistically similar to each other). Different letters denote statistical significance, p < 0.05. Values presented as mean ± SEM. b Remodeling index measured as percent change from NP-C (n = 12) lumen diameters at 80 mm Hg. NP-L (n = 10) and NP-L+H (n = 6) had negative indicies (reduction in lumen diameter), while LP-C (n = 12), LP-L (n = 15), and LP-L+H (n = 12) were positive. Note the correlation between percent tone (shown in a) and remodeling index in the pregnant groups, and the absence of this correlation in the nonpregnant groups.

Fig. 3

a Passive lumen diameters (mean ± SEM) of uterine radial arteries (RA) from all groups measured at 80 mm Hg in a relaxing solution containing 100 μM papaverine and 10 μM diltiazem. Note the approximately 35% increase in lumen diameter in the LP-C vs. NP-C groups that is indicative of expansive remodeling. Different letters denote statistical significance (p < 0.05); the same letter denotes statistical similarity (p ≥ 0.05). b Wall thickness of the same arteries as in a at 80 mm Hg. Values presented as mean ± SEM. Different letters denote statistical significance (p < 0.05); the same letter denotes statistical similarity (p ≥ 0.05). For both a and b, n values are: NP-C 12, NP-L 10, NP-L+H 6, LP-C 12, LP-L 15, LP-L+H 12.

Fig. 4

a Positive correlation between mean arterial pressure (mm Hg) and level of tone (%) at 80 mm Hg in vessels from all nonpregnant groups (r² = 0.74, p = 0.013). b Absence of correlation between mean arterial pressure and tone (%) at 80 mm Hg in all late pregnant groups (r² = 0.04, p > 0.05).