Effect of cortisol on fetal ovine vascular angiotensin II receptors and contractility.
The renin angiotensin system is important in the regulation of fetal blood pressure. This study investigated the expression of angiotensin AT(1) and AT(2) receptors in the ovine fetal heart, aorta and umbilical artery, and how these receptors are affected by cortisol. Cortisol infusion into the fetus has previously been shown to cause an increase in fetal blood pressure. We hypothesised that this effect of cortisol is mediated by upregulation of the angiotensin AT(1) receptor. Binding studies performed on tissues with intact endothelium demonstrated both receptor subtypes in the fetal aorta and right ventricle, although the latter contained mainly angiotensin AT(2) receptors. In contrast, only angiotensin AT(1) receptors were found in the umbilical artery. Cortisol infusion into fetuses (3 mg/day for 3-5 days) caused a physiological increase in plasma cortisol levels to 29+/-4 nM. This was associated with an increase in systolic pressure (57.8+/-1.7 vs. 52.2+/-1.5 mm Hg, P<0.05), but cortisol had no effect on the density or affinity of angiotensin receptors, nor on the in vitro contractile responses of carotid and umbilical arterial rings to 5-microM angiotensin II. In conclusion, this study has demonstrated differential expression of angiotensin AT(1) and AT(2) receptors in the different regions of the ovine fetal cardiovascular system and that the angiotensin AT(1) receptor is functional. The lack of any effect of low doses of cortisol on these receptors and on the contractility of isolated fetal vessels to angiotensin II suggests cortisol acts by other mechanisms to raise fetal arterial pressure.
Hegarty
B D
BD
School of Physiology and Pharmacology, University of New South Wales, NSW 2052, Sydney, Australia.
Burrell
J H
JH
Gibson
K J
KJ
McMullen
J R
JR
Lumbers
E R
ER
D015059:1-Sarcosine-8-Isoleucine Angiotensin II / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D005333:Fetus / Q000187:drug effects*; D006854:Hydrocortisone / Q000494:pharmacology*; D066298:In Vitro Techniques; D011247:Pregnancy; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000032:analysis / Q000187:drug effects* / Q000502:physiology; D012756:Sheep; D014661:Vasoconstriction / Q000187:drug effects*
D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D015059:1-Sarcosine-8-Isoleucine Angiotensin II; D006854:Hydrocortisone