Geniposidic acid upregulates atrial natriuretic peptide secretion and lowers blood pressure in spontaneously hypertensive rats

Cytochrome P450 (CYP)-derived epoxyeicosatrienoic acids (EETs) have potent vasodilatory and diuretic feature, and therefore potentially hypotensive effect. No in vivo studies, however, were performed to support it. This study investigated the hypothesis via overexpressing CYP epoxygense genes in spontaneously hypertensive rats (SHR). Recombinant adeno-associated virus vector (rAAV) was utilized to mediate long-term transfection of CYP2J2 and CYP2C11 genes, respectively, in adult SHR, and animal systolic blood pressure (SBP) was monitored using arterial caudilis indirect manometric method. Results showed that at 2 months the urinary excretion of stable hydrolysis metabolic product of 14, 15-EE, 14–15-DHET increased by 11 and 8.7 folds in rAAV-2J2 and rAAV-2C11 groups, respectively, compared with AAV-GFP-treated rats. (2) SBP in 2J2- and 2C11-treated rats decreased from 175.0 ± 2.8mHg to 163.5 ± 5.8mmHg and 161.2 ± 6.1 mmHg, respectively, ( p <0.01) at month 2, and it is 165.0 ± 4.7 mmHg and 173.0 ± 12.8 mmHg at month 6 after gene injection (~30mmHg and ~23mmHg lowerer than that in control animals, respectively, p <0.001). (3) Before the rats were sacrificed, cardiac function tests with Pressure-Volume System showed that maximum intracardiac pressure was 202.1 ± 30.0 & 209.1 ± 17.1mmHg in two gene-treated rats, respectively, significantly lower than control (241.2 ± 18.2mmHg, p <0.01) and cardiac output in treatment rats were significantly higher than control (p<0.05). (4) Interestingly, atrial natriuretic peptide (ANP) mRNA were up-regulated 6–14 folds respectively in myocardium of 2J2 and 2C11 groups; furthermore, C-type receptor mRNA of ANP was increased in heart, lung, kidney and aorta. (5) in cultured atrial cells (HLB2G5), exogenous EETs stimulated ANP production. In conclusions, for first time our data indicates overexpression of CYP2J2 or CYP2C11 could prevent development of hypertension in SHR, improve cardiac functions, which may involve up-regulating ANP expression and its receptors in target tissues, which suppresses collagen deposition and cardiovascular remodeling.

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Involvement of atrial natriuretic peptide in blood pressure reduction induced by estradiol in spontaneously hypertensive rats

Regulatory Peptides ◽

10.1016/j.regpep.2003.10.007 ◽

2004 ◽

Vol 117 (1) ◽

pp. 53-60 ◽

Cited By ~ 23

Author(s):

Najara O. Belo ◽

Juliana Silva-Barra ◽

Evelin C. Carnio ◽

Jose Antunes-Rodrigues ◽

Jolanta Gutkowska ◽

...

Keyword(s):

Blood Pressure ◽

Atrial Natriuretic Peptide ◽

Natriuretic Peptide ◽

Spontaneously Hypertensive Rats ◽

Blood Pressure Reduction ◽

Pressure Reduction ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Atrial Natriuretic

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Renal actions of atrial natriuretic peptide in spontaneously hypertensive rats: the role of nitric oxide as a key mediator

AJP Renal Physiology ◽

10.1152/ajprenal.00624.2011 ◽

2012 ◽

Vol 302 (11) ◽

pp. F1385-F1394 ◽

Cited By ~ 5

Author(s):

Rosana Elesgaray ◽

Carolina Caniffi ◽

Lucía Savignano ◽

Mariana Romero ◽

Myriam Mac Laughlin ◽

...

Keyword(s):

Nitric Oxide ◽

Blood Pressure ◽

Atrial Natriuretic Peptide ◽

Natriuretic Peptide ◽

Spontaneously Hypertensive Rats ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Calmodulin Inhibitors ◽

Nos Isoforms ◽

Atrial Natriuretic

Atrial natriuretic peptide (ANP) is an important regulator of blood pressure (BP). One of the mechanisms whereby ANP impacts BP is by stimulation of nitric oxide (NO) production in different tissues involved in BP control. We hypothesized that ANP-stimulated NO is impaired in the kidneys of spontaneously hypertensive rats (SHR) and this contributes to the development and/or maintenance of high levels of BP. We investigated the effects of ANP on the NO system in SHR, studying the changes in renal nitric oxide synthase (NOS) activity and expression in response to peptide infusion, the signaling pathways implicated in the signaling cascade that activates NOS, and identifying the natriuretic peptide receptors (NPR), guanylyl cyclase receptors (NPR-A and NPR-B) and/or NPR-C, and NOS isoforms involved. In vivo, SHR and Wistar-Kyoto rats (WKY) were infused with saline (0.05 ml/min) or ANP (0.2 μg·kg−1·min−1). NOS activity and endothelial (eNOS), neuronal (nNOS), and inducible (iNOS) NOS expression were measured in the renal cortex and medulla. In vitro, ANP-induced renal NOS activity was determined in the presence of iNOS and nNOS inhibitors, NPR-A/B blockers, guanine nucleotide-regulatory (Gi) protein, and calmodulin inhibitors. Renal NOS activity was higher in SHR than in WKY. ANP increased NOS activity, but activation was lower in SHR than in WKY. ANP had no effect on expression of NOS isoforms. ANP-induced NOS activity was not modified by iNOS and nNOS inhibitors. NPR-A/B blockade blunted NOS stimulation via ANP in kidney. The renal NOS response to ANP was reduced by Gi protein and calmodulin inhibitors. We conclude that ANP interacts with NPR-C, activating Ca-calmodulin eNOS through Gi protein. NOS activation also involves NPR-A/B. The NOS response to ANP was diminished in kidneys of SHR. The impaired NO system response to ANP in SHR participates in the maintenance of high blood pressure.

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Effects of Moxibustion on Blood Pressure and Renal Function in Spontaneously Hypertensive Rats

The American Journal of Chinese Medicine ◽

10.1142/s0192415x97000056 ◽

1997 ◽

Vol 25 (01) ◽

pp. 21-26 ◽

Cited By ~ 11

Author(s):

Ho Sub Lee ◽

Yun Cho Yu ◽

Seong Tae Kim ◽

Kyung Sik Kim

Keyword(s):

Blood Pressure ◽

Renal Function ◽

Atrial Natriuretic Peptide ◽

Systolic Blood Pressure ◽

Natriuretic Peptide ◽

Plasma Levels ◽

Spontaneously Hypertensive Rats ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Atrial Natriuretic

The aim of this study was to investigate the effects of moxibustion at the meridian points BL-15 (Xin-shu) and BL-27 (Xiao-chang-shu) on renal function, systolic blood pressure, plasma levels of renin activity, aldosterone and atrial natriuretic peptide in spontaneously hypertensive rats. The results showed that urine volume increased significantly after moxibustion at the meridian points BL-15, but decreased at BL-27. Urinary excretion of Na + decreased after moxibustion at the meridian points BL-15 and BL-27. Systolic blood pressure decreased after moxibustion at the meridian point BL-15. No effect was observed at BL-27. Plasma levels of aldosterone and renin activity increased significantly, but the levels of atrial natriuretic peptide decreased significantly after moxibustion at BL-15. Plasma levels of aldosterone and atrial natriuretic peptide increased significantly after moxibustion at the meridian points BL-27. These results suggest that the meridian points BL-15 and BL-27 are related to the regulation of renal function and the secretion of hormone with body fluid metabolism.

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