Maternal adaptation in pregnant hypertensive rats: improvement of vascular and inflammatory variables and oxidative damage in the kidney.
BACKGROUND
Mechanisms of normalization of blood pressure in spontaneously hypertensive rats (SHR) during pregnancy were investigated. We hypothesized that at the end of pregnancy (20th day), the modified renal renin-angiotensin system (RAS) plays a pivotal role in this effect associated with reduced inflammation and oxidative damage.


METHODS
We measured blood pressure and heart rate (HR) using a noninvasive tail-cuff method in conscious SHR and Wistar Kyoto rats (WKY). Nonpregnant (-NP) or pregnant (-P) SHR and WKY were used to compare the changes of angiotensin II (ANG II) type 1 (AT1) and type 2 (AT2) receptor expression in the kidney. Renal modification of proinflammatory enzyme expression, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) and their transcription factor nuclear factor-kappaB (NF-kappaB) were also evaluated. Renal malonyldialdehyde (MDA) content and protein nitrotyrosylation, as indicators of oxidative stress, were assessed. Moreover monocyte chemotactic protein-1 (MCP-1) mRNA was determined.


RESULTS
Our findings indicate that the significant reduction of blood pressure induced by pregnancy in the SHR strain could be related to reduced AT1 and increased AT2 expression. We also saw a significant decline in renal NF-kappaB, COX-2, iNOS, and macrophage infiltration, as well as the fall in oxidative stress indicators.


CONCLUSIONS
The increased proinflammatory and oxidative variables, seen in SHR, are strongly ameliorated by pregnancy. In pregnant SHR animals, the adaptive and compensative changes of RAS and inflammation in the kidney seem to contribute to the reduction of blood pressure near term.
Iacono
Anna
A
Department of Experimental Pharmacology, University of Naples Federico II, Naples, Italy.
Bianco
Giuseppe
G
Mattace Raso
Giuseppina
G
Esposito
Emanuela
E
d'Emmanuele di Villa Bianca
Roberta
R
Sorrentino
Raffaella
R
Cuzzocrea
Salvatore
S
Calignano
Antonio
A
Autore
Giuseppina
G
Meli
Rosaria
R
D000222:Adaptation, Physiological; D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D018932:Chemokine CCL2 / Q000096:biosynthesis; D051546:Cyclooxygenase 2 / Q000502:physiology; D005260:Female; D006339:Heart Rate / Q000502:physiology; D006973:Hypertension / Q000503:physiopathology*; D020672:I-kappa B Proteins / Q000502:physiology; D007668:Kidney / Q000503:physiopathology*; D015227:Lipid Peroxidation; D008315:Malondialdehyde / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D052247:Nitric Oxide Synthase Type II / Q000502:physiology; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000503:physiopathology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology; D044139:Receptor, Angiotensin, Type 2 / Q000502:physiology; D051996:Transcription Factor RelA / Q000502:physiology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000096:biosynthesis
C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D020672:I-kappa B Proteins; C000606206:Nfkbia protein, rat; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; C002744:3-nitrotyrosine; D014443:Tyrosine; D008315:Malondialdehyde; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat