Cardiovascular and renal effects of ANG II and NO in the newborn: roles of AT1Rs and /or AT2Rs

The vasoactive factors angiotensin II (ANG II) and nitric oxide (NO), and the balance between them play a major role in regulating cardiovascular and electrolyte homeostasis. During the perinatal period, both factors are elevated, yet their physiological roles have not been clearly defined. Furthermore, the temporal and spatial expression of the receptors for ANG II (AT1Rs and AT2Rs) is developmentally regulated, although their physiological roles are also unknown. The present study aimed to elucidate for the first time, the physiological effects of ANG II on the kidney during postnatal maturation, as well as the potential role of the ATRs in initiating these physiological effects. In addition, this study investigated for the first time the interaction between ANG II and NO in regulating cardiovascular and renal function during the period of adaptation of the newborn to life after birth. Two study protocols were carried out in conscious lambs at two stages of postnatal maturation - one and six weeks. The first protocol evaluated (a) the individual functions of ATRs and (b) any possible interaction between them in mediating haemodynamic and renal physiological responses of ANG II. The second protocol investigated the roles of ATRs in modulating physiological roles of endogenoulsy produced NO during development. Results from these experiments show for the first time, that there does not appear to be any interaction between AT1Rs and AT2Rs in mediating haemodynamic effects of endogenous ANG II early in life. In contrast, the renal effects of ANG II are mediated through AT1Rs in an age-dependent manner, whereas AT2Rs buffer these effects. My research also shows for the first time, that ANG II modulates the effects of NO on renal haemodynamics and function but not systemic haemodynamics in an age-dependent manner through activation of AT1Rs and AT2Rs. Furthermore, it appears that AT2Rs interact with AT1Rs in mediating the renal effects of NO in developing newborn animals. This is the first description of renal effects of ANG II and a new and important interaction between ANG II and NO under physiological conditions early in life.

Name thesis:degree_name

Doctor of Philosophy (PhD)

Discipline thesis:degree_discipline

Medical Science

Grantor dc:publisher.institution

Graduate Studies

Year dc:date.issued

2012

Author dc:creator

• Vinturache, Angela Elena

Advisor dc:contributor.advisor

• Smith, Francine Gabriel

• Physiology

Statement dc:rights

• University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.

Language dc:language.iso

eng

DOI

http://dx.doi.org/10.11575/PRISM/25214

OAI identifier oai:identifier

oai:ucalgary.scholaris.ca:11023/113