Angiotensin is vital in pregnancy For blood to the fetus to be shunted It drives the volume expansion But its pressor responses are blunted
Last weekend it was Mothering Sunday, which prompted my to write this little number in honour of my mother1.
With the onset of pregnancy there are a number of haemodynamic adaptations that occur in the maternal cardiovascular system. In general, these adaptations occur in order to meet the additional metabolic demands on the mother and sustain the growing fetus. Indeed if you think about it, the mother now has to perfuse a whole new, metabolically active organ during gestation2. As a result these haemodynamic changes are vital for a successful pregnancy. The failure of these adaptations to fully occur may reduce blood flow to the fetus, challenging fetal development and possibly leading to maternal complications.
Occurring very early in gestation, the first adaptation to occur is a substantial fall in total peripheral resistance. Indeed, occurring as early as it does, the fall in peripheral resistance is vital and is thought to drive the subsequent adaptations.
Following the fall in total peripheral resistance there is a large increase in maternal plasma and blood volume, driven by increased Na+ reabsorption and erythropoiesis. Subsequently, as pregnancy develops, there is a marked increase in cardiac output via an increase in stroke volume and heart rate. The increased blood flow to the uteroplacental unit in pregnancy correlates to the increases in cardiac output and plasma volume highlighting the importance of these haemodynamic adaptations to a successful pregnancy.
Angiotensin II (Ang II) is the active part of the renin-angiotensin system3. Ang II is a potent vasoconstrictor and also has a role in Na+ balance directly and via the stimulation of aldosterone. During pregnancy, oestrogen increases plasma concentrations of renin, angiotensinogen, Ang II and aldosterone4. It is due to these oestrogen-mediated increases in Ang II and aldosterone that drive Na+ retention and plasma volume expansion.
The decrease in peripheral resistance is in part mediated by an imbalance in the vasoconstrictor/vasodilator pathways, not just that of Ang II. This too may involve the increase in circulating oestrogen. By early in pregnancy the vasopressor response of Ang II is markedly attenuated; whilst similar responses are see to catecholamines such as noradrenaline and phenylephrine. This is matched by enhanced endothelium-dependent vasodilatation via the increased release of endothelial-derived relaxing factors such as nitric oxide (NO), prostacyclin (PGI2) and the endothelium-derived hyperpolarising factor(s) (EDHF)5.
The increased release of NO, PGI2 and EDHF during pregnancy is linked to circulating oestrogen. The influence of oestrogen on vasoconstriction and vasodilatation can be observed through the normal menstrual cycle with NO, PGI2 and EDHF-mediated vasodilatation all waxing and waning through the duration of the cycle. Not only does this increase vasodilatation, but it also goes some way to explaining the attenuated response to Ang II. For Ang II, it is the increased prostaglandins that appear to be particularly important for the blunted response, but teasingly this appears to be independent of oestrogen (or progesterone).
So there you go, Ang II (and aldosterone) drive plasma expansion but the blunted vasopressor response of Ang II is vital for the initial drop in peripheral resistance in early pregnancy.
- It is not true to say this was in place of a card, but I did subsequently forget to get one.
- Ok, fair enough, obviously the uterus was there prior to conception but it was hardly pulling the same proportion of blood flow. I am generally referring to the conceptus as a whole here.
- OK, there are a number of active angiotensin peptides including; Ang III, Ang IV, Ang 1-7 etc.
- The increased erythropoiesis however, is due to the erythropoietic effect of progesterone not oestrogen
- I think there is a distinction to be made about whether this is a name (there is an EDHF) or whether it is a description. There is more than one factor that is derived from the endothelium and hyperpolarises the underlying smooth muscle, but not all fit the characterisation for the original EDHF.