Chronic Infusion of Low Doses of Atrial Natriuretic Factor (ANF Arg 101-Tyr 126) Reduces Blood Pressure in Conscious SHR without Apparent Changes in Sodium Excretion

García, Raúl; Thibault, Gaétan; Gutkowska, Jolanta; Horký, K; Hamet, Pavel; Cantin, M.; Genest, Jacques

doi:10.3181/00379727-179-rc1aa

Cited by 92 publications

(31 citation statements)

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“…The RIA can equally recognize a-ANP [17][18][19][20][21][22][23][24][25][26][27][28], a-rANP, a-hANP, arANP , a-rANP , and a-rANP . The lowest detectable concentration of ANP was 1 pg/tube and the amount of 50% binding inhibition (IC50) was 25 pg/tube.…”

Section: Methodsmentioning

confidence: 99%

“…Plasma ANP concentrations in rats were determined by the RIA with a rabbit polyclonal antiserum raised against a COOH-terminal fragment of a-ANP, a-ANP [17][18][19][20][21][22][23][24][25][26][27][28], as described previously in details (31). The RIA can equally recognize a-ANP [17][18][19][20][21][22][23][24][25][26][27][28], a-rANP, a-hANP, arANP , a-rANP , and a-rANP .…”

Section: Methodsmentioning

confidence: 99%

“…These findings suggest that augmented secretion of ANP plays a compensatory role in the maintenance of blood pressure. In addition, an infusion of ANP (5-100 ng/kg per min) for a couple of days to a week caused a reduction in blood pressure in SHR; rats with onekidney, one-clip or two-kidney, one-clip renal hypertension; or angiotensin II-or norepinephrine-infused rats (21,22), without consistent changes in urine volume or urinary excretion of sodium. In patients with essential hypertension, a bolus injection (50-100 ,ug) or an infusion (1 ug/min) of relatively high doses of ANP caused rises in urine volume and sodium excretion and a fall in arterial pressure (23,24).…”

Section: Introductionmentioning

confidence: 99%

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Chronic blockade of endogenous atrial natriuretic polypeptide (ANP) by monoclonal antibody against ANP accelerates the development of hypertension in spontaneously hypertensive and deoxycorticosterone acetate-salt-hypertensive rats.

Itoh¹,

Nakao²,

Mukoyama³

et al. 1989

J. Clin. Invest.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Chronic blockade of endogenous atrial natriuretic polypeptide (ANP) by monoclonal antibody against ANP accelerates the development of hypertension in spontaneously hypertensive and deoxycorticosterone acetate-salt-hypertensive rats.

Itoh¹,

Nakao²,

Mukoyama³

et al. 1989

J. Clin. Invest.

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“…These results indicate that blood pressure was actually lower in the HT than the HC group at the end of treatment. Garcia et al 5 have reported that long-term infusion of ANP (300 ng/kg body wt per hour) for 7 days in conscious SHRs and WKYs induced a drop of the initial SBP in SHRs. Using a lower dose of ANP (100 ng/kg body wt per hour), Cachofeiro et al 34 reported a fall in arterial pressure 5 days after beginning the ANP infusion in SHRs.…”

Section: \ Figure 9 Photomicrographs Of Typical Examples Of Longitudmentioning

confidence: 99%

Effect of a nonhypotensive long-term infusion of ANP on the mechanical and structural properties of the arterial wall in Wistar-Kyoto and spontaneously hypertensive rats.

Grand

Poitevin

Benessiano

et al. 1993

Arterioscler Thromb

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A nonhypotensive dose of atrial natriuretic peptide (ANP) was infused (60 pg/kg body wt per day s.c. by osmotic pump) for 25 days in 16-week-old normotensive Wistar-Kyoto rats (WKYs, TI = 12) and age-matched spontaneously hypertensive rats (SHRs, n = 12). During the infusion period, systolic blood pressure, urinary volume, and cyclic guanosine monophosphate (cGMP) excretion/12 hr were measured once a week in both groups. Then mechanical and morphological properties of the arterial wall and plasma ANP levels were assessed and compared with those from control groups of SHRs («=8) and WKYs (n=8) receiving a saline vehicle. The compliance (CC) of the in situ localized carotid artery was measured for pressures ranging from 25 to 175 mm Hg under control conditions and after "poisoning" of smooth muscle tone by potassium cyanide. After pressure fixation, the medial thickness, elastin and collagen contents, and the size and number of nuclei were measured in the thoracic descending aorta. In WKYs, ANP did not modify either mechanical or structural properties of the arterial wall or biochemical parameters. Conversely, in ANP-treated SHRs, CC was significantly increased compared with untreated SHRs under basal conditions (p<0.03) and after potassium cyanide poisoning (/><0.02). Structural properties were also modified by ANP in SHRs, i.e., medial thickness (129.3±4.1 versus 113.1 ±3.3 jum, p<0.01) and nuclear size (8.81 ±0.28 versus 5.52±0.20 /i.m\p<0.0001) in untreated and treated SHRs, respectively. Furthermore, urinary volume and cGMP content were significantly increased during ANP infusion in treated SHRs (p<0.05). The present results indicate concomitant modifications of mechanical and structural properties of the arterial wall in SHRs chronically treated with low doses of ANP. These long-term effects of ANP could be involved in the remodeling of the arterial wall observed during hypertension and could have beneficial effects on cardiovascular diseases in chronic sustained hyperten- fects such as an increase of diuresis, natriuresis, J. JL urinary excretion of cyclic guanosine monophosphate (cGMP), and glomerular filtration rate and a selective regional relaxation of vascular smooth muscle cells 1 that is partially mediated by the activation of particulate guanylate cyclase via its second messenger, cGMP. The vasorelaxant effects of ANP have been extensively demonstrated in in vitro preparations 2 -4 but not so much in in vivo models. Recent studies have demonstrated that long-term infusion of ANP at low doses reduces blood pressure in several animal models of hypertension, including spontaneously hypertensive rats (SHRs). 5 -8 In this strain, it has been previously shown that the antihypertensive properties were more Received August 13, 1992; revision accepted October 30, 1992. marked when the plasma levels of ANP were modestly but chronically elevated than when they were markedly and acutely increased. 8In SHRs, elevated systemic resistances are associated with an increase in arteriolar and arterial wall thickne...

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“…In target tissues such as kidney and endothelial cells, the active α-ANP peptide signals by binding its specific receptor, NPR-A, which increases intracellular cGMP levels and decreases blood pressure by lowering systemic vascular resistance and increasing renal salt excretion, two effects aided by inhibition of the renin-angiotensinaldosterone pathway. Infusion of ANP has been demonstrated to decrease blood pressure in hypertensive patients (18,19) and animal models (20,21), but long-term systemic expression of ANP would be required to control blood pressure. Although systemic ANP delivery and a decrease in blood pressure has been achieved following i.v.…”

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confidence: 99%

A gene therapy approach for long-term normalization of blood pressure in hypertensive mice by ANP-secreting human skin grafts

Therrien

Kim

Terunuma

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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The use of bioengineered human skin as a bioreactor to deliver therapeutic factors has a number of advantages including accessibility that allows manipulation and monitoring of genetically modified cells. We demonstrate a skin gene therapy approach that can regulate blood pressure and treat systemic hypertension by expressing atrial natriuretic peptide (ANP), a hormone able to decrease blood pressure, in bioengineered human skin equivalents (HSE). Additionally, the expression of a selectable marker gene, multidrug resistance (MDR) type 1, is linked to ANP expression on a bicistronic vector and was coexpressed in the human keratinocytes and fibroblasts of the HSE that were grafted onto immunocompromised mice. Topical treatments of grafted HSE with the antimitotic agent colchicine select for keratinocyte progenitors that express both MDR and ANP. Significant plasma levels of human ANP were detected in mice grafted with HSE expressing ANP from either keratinocytes or fibroblasts, and topical selection of grafted HSE resulted in persistent high levels of ANP expression in vivo. Mice with elevated plasma levels of human ANP showed lower renin levels and, correspondingly, had lower systemic blood pressure than controls. Furthermore, mice with HSE grafts expressing human ANP did not develop elevated blood pressure when fed a high-salt diet. These findings illustrate the potential of this human skin gene therapy approach to deliver therapeutic molecules systemically for long-term treatment of diverse diseases.keratinocytes | human engineered skin | hypertension | multi-drug resistance gene | retroviral vectors A lthough skin can be easily accessed for manipulation, a major challenge of using skin gene therapy to treat systemic diseases has been the difficulty of achieving sustained expression of desired therapeutic genes in a high percentage of keratinocytes (Kc) (1-8), in part because few good markers of Kc stem cells exist for isolation and gene targeting (9-13). Previously, we described how topical colchicine treatment of human skin equivalents (HSE) containing Kc engineered to express the multidrug resistance (MDR) gene could select and enrich for MDR-expressing human Kc progenitor cells because only MDRexpressing Kc were able to pump-out the antimitotic inhibitor and proliferate (5). However, the therapeutic utility of this gene therapy approach in treating systemic diseases was unproven.Gene therapy strategies that have been discussed for the treatment of hypertension include overexpression of genes such as atrial natriuretic peptide (ANP) that are relevant in reducing blood pressure (14,15). ANP is a 126-amino acid peptide hormone synthesized mainly by right atrial cardiomyocytes as an inactive precursor (pro-ANP) (Fig. S1). Pro-ANP is secreted and converted into an active ANP peptide of 28 amino acids (α-ANP) by corin receptors located on the cell surface of cardiomyocytes (16, 17) in response to volume expansion and increases in venous pressure. In target tissues such as kidney and endothelial cells, the active...

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Chronic Infusion of Low Doses of Atrial Natriuretic Factor (ANF Arg 101-Tyr 126) Reduces Blood Pressure in Conscious SHR without Apparent Changes in Sodium Excretion

Cited by 92 publications

References 0 publications

Chronic blockade of endogenous atrial natriuretic polypeptide (ANP) by monoclonal antibody against ANP accelerates the development of hypertension in spontaneously hypertensive and deoxycorticosterone acetate-salt-hypertensive rats.

Chronic blockade of endogenous atrial natriuretic polypeptide (ANP) by monoclonal antibody against ANP accelerates the development of hypertension in spontaneously hypertensive and deoxycorticosterone acetate-salt-hypertensive rats.

Effect of a nonhypotensive long-term infusion of ANP on the mechanical and structural properties of the arterial wall in Wistar-Kyoto and spontaneously hypertensive rats.

A gene therapy approach for long-term normalization of blood pressure in hypertensive mice by ANP-secreting human skin grafts

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