Professor John F Laycock

My primary research interest is focussed on the posterior pituitary hormone vasopressin (VP) and its actions/interactions in both brain and periphery. Much of my recent work falls into 2 main areas a) VP effects on the cardiovascular system, and b) VP renal actions.

a) Cardiovascular effects of VP

Until quite recently, we maintained a colony of Brattleboro rats at CX, and these unique animals were an important experimental model for us since they have a genetic defect which results in a total absence of circulating VP and consequently they suffer from the condition known as diabetes insipidus (DI). Using this animal model we have been able to study the cardiovascular effects of VP by developing an implanted system allowing us to record not only the arterial (and central venous) blood pressures and heart rate, but also the cardiac output using the thermodilution principle. This allows us then to determine what happens to the total peripheral resistance to blood flow as well as the heart’s stroke volume. For example, one specific interaction we have studied is between VP and gonadal steroids. We found that blood pressure recovery following a large haemorrhage (a potent stimulus for VP release) is significantly better in male rats (and female rats during those days of their oestrous cycle when gonadal asteroid levels are low) than in female rats in pro-oestrus when the circulating oestrogen and progesterone levels are high. Interestingly, this difference is absent in Brattleboro DI rats. Ovariectomy followed by replacement of the gonadal steroids has so far failed to identify whether the effect is due specifically to one or other of the steroids being produced during pro-oestrus.

b) Renal actions/interactions of VP

Following our cardiovascular studies on the interactions between VP and the gonadal steroids we studied the effect of another hormone released in large amounts during pro-oestrus, prolactin (PRL) and while we failed to uncover any involvement with the cardiovascular effect of VP, we did fid a remarkable difference in renal response to PRL between Brattleboro DI rats and control animals. In essence, in the presence of circulating VP, PRL seems to exert a mild diuretic effect, while in the absence of VP it has a profound antidiuretic effect. This interesting interaction is one we wish to study in further detail as there may well be clinical implications during pregnancy and lactation, for instance.

I have also been involved in molecular and cellular studies on the antidiuretic action of VP, for instance in collaboration with Dr. Jacques Hanoune (INSERM, Paris). This involved studies on mRNA for the renal VP V2 receptor, four of the cAMP isoforms present in kidneys and G protein components.

It is hoped that some of the in vivo techniques applied above can be used to study the involvement of annexin1 in glucocorticoid-related cardiovascular and renal effects using annexin 1 knockout mice, in collaboration with Professor Buckingham.

Active research is currently on hold as other duties prevail.

Selected references:

1. Morrissey,SE, Baden-Fuller,J, Murugananthan,N, Whitehead,SA & Laycock,JF (1996). Influence of oestrous cycle on the pressor recovery following haemorrhage in anaesthetized Brattleboro rats. Eur. J. Endocrinol., 134, 379-385.

2. Morrissey, SE, Edwards, TJ, Wilson, KJ, Whitehead, SA & Laycock, JF (1997). Effect of ovariectomy and steroid hormone replacement on the recovery of arterial blood pressure following haemorrhage in anaesthetized Brattleboro rats. Eur. J. Endocrinol., 136: 330-337 

 

3. Shen, T, Laycock, JF, Suzuki, Y, Defer, N & Hanoune, J (1998). Stability of the vasopressin V2 receptor-adenylyl cyclase system in rat kidney. Eur. J. Pharmacol., 341: 87-94

4. Wargent, ET, Burgess, WJ, Laycock, JF & Balment, RJ (1999). Separate receptors mediate oxytocin and vasopressin stimulation of cAMP in rat inner medullary collecting duct cells. Exp. Physiol., 84, 17-25