Role of nitric oxide in the attenuated pressor responses of pregnant or sodium-deplete sheep.
Reduced pressor responsiveness to angiotensin II (Ang II) during pregnancy and sodium depletion is a well-known but little understood phenomenon; whether the same mechanisms are involved in both situations is unclear. In pregnant humans, altered vascular reactivity to norepinephrine (NE) has also been demonstrated. Nitric oxide (NO) has been implicated in the modulation of blood pressure (BP) and the maintenance of vascular tone and may be involved in these attenuated responses. We examined the role of NO in the pressor responses to (a) Ang II (5, 10, 25, 50 micrograms/h) and NE (0.32, 0.65, 1.62, 3.24 mg/h) in pregnant and postpartum sheep, and (b) to Ang II (5, 7, 5, 10, 25, 50 micrograms/h) in sodium-replete sheep and sheep made sodium deplete by 24 h of parotid salivary drainage. Vascular NO production was inhibited by pretreatment with N omega-nitro-L-arginine (NOLA 10 mg/kg), a NO-synthase inhibitor. Pregnancy significantly reduced (p < 0.001) pressor responses to Ang II, which ranged from 5.1 +/- 0.2-30.6 +/- 1.2 mm Hg as compared with postpartum increases of 10.3 +/- 0.5-52.2 +/- 3.4 mm Hg. Pretreatment with NOLA partially restored Ang II responses to postpartum levels. Pregnancy did not alter pressor responses to NE. Sodium depletion also significantly reduced responses to Ang II by the same amount as in pregnancy, and these responses returned to normal with pretreatment with NOLA. NO thus has a role in modulating the attenuated pressor responses to Ang II in pregnant and sodium-deplete sheep.
Tresham
J J
JJ
Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria, Australia.
Boutros
P
P
Wintour
E M
EM
May
C N
CN
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D049590:Postpartum Period / Q000502:physiology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D012756:Sheep / Q000502:physiology*; D012964:Sodium / Q000172:deficiency*
D004791:Enzyme Inhibitors; D000804:Angiotensin II; D019335:Nitroarginine; D009569:Nitric Oxide; D012964:Sodium; D019001:Nitric Oxide Synthase; D009638:Norepinephrine