Synthetic atrial natriuretic factor does not dilate resistance-sized arteries.

Osol, George; Halpern, William; Tesfamariam, Belay; Nakayama, Kensyo; Weinberg, Daniel I.

doi:10.1161/01.hyp.8.7.606

Cited by 43 publications

(15 citation statements)

References 6 publications

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“…Moreover, a vasorelaxant effect on the resistance vessels has been recently denied in vitro. 15 Conceivably, an angiotensin II or norepinephrine precontracted state of the vasculature is needed for ANF to exert a vasodilatory effect in vivo as described in vitro.8,9 Our patients were in the higher part of the range of the normal sodium diet (about 170 meq/24 hr) and studied while in the recumbent position. Therefore, neither the renin-angiotensin system nor the sympathetic nervous system was particularly activated.…”

Section: Discussionmentioning

confidence: 96%

Low-dose infusion of atrial natriuretic factor in mild essential hypertension.

et al. 1989

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Intra-arterial blood pressure, cardiac output, heart rate, right heart indexes, urinary electrolytes, and urinary volume were monitored in eight patients with untreated (WHO Class I) essential hypertension. The patients were given synthetic atrial natriuretic factor (ANF) (99-126 a -hANP) at 1 and 2 pmol/kg/min in series (phases 1 and 2, 2 hours each dose) or vehicle (hemaccel) in random order on two separate occasions while on their usual diet. Arterial plasma ANF levels increased significantly from basal and time-matched placebo values from 25±2 and 28+3 pmol /1 to 50±4 and 83±9 pmol/l at the end of phases 1 and 2, respectively (p<0.001). After 30 minutes during phase 2, systolic blood pressure decreased significantly by 20±4 mm Hg (p<0.001) from basal and time-matched placebo values and remained significantly reduced (-17±4 mm Hg,p<0.001) by the end of the recovery period (2 hours after infusions were completed). Pulmonary systolic blood pressure decreased by 5±1 mm Hg (phase 2,p<0.05). Cardiac output decreased by 0.5 ±0.1 1/min below baseline at the end of phase 2 ofANF infusion, whereas it increased significantly (p<0.02) by 0.6±0.1 1/min during vehicle infusion. Systemic diastolic, pulmonary diastolic, right atrial, and wedge pressures were not significantly changed during ANF or vehicle infusions, nor were pulmonary vascular resistance or heart rate altered. Systemic vascular resistance did not change significantly during both infusions, whereas during recovery, systemic vascular resistance decreased significantly after ANF infusion was discontinued (p<0.05). Microhematocrit levels increased dose dependently during ANF. The maximum increase was observed at the end of phase 2 (+4.7±1.7%), whereas the microhematocrit level decreased to -2.4±0.6% with vehicle (p<0.001) at the end of phase 2. Urinary sodium excretion increased significantly (p<0.02) by the end of phase 2 under ANF infusion (+38±15%), whereas it decreased (-10±6%) under placebo infusion by the end of phase 2. Urinary magnesium excretion was significantly increased during ANF infusion from phase 1 (p<0.02), whereas urinary potassium levels, calcium levels, creatinine levels, volume, and glomerular filtration rate did not difer significantly between the two infusions. Plasma renin, angiotensin H, aldosterone, and catecholamine concentrations did not change significantly during ANF or vehicle infusions. Our data suggest that increases in circulating arterial ANF levels to the upper limit of the ranges reported for humans with hypertension in absence of cardiac or renal failure reduce plasma volume and exert a selective lowering effect on systolic blood pressure without changing calculated peripheral vascular resistances. (Circulation 1989;80:893-902

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Section: Discussionmentioning

confidence: 96%

Low-dose infusion of atrial natriuretic factor in mild essential hypertension.

et al. 1989

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“…On the other hand, a role of larger arterial vessels in the decrease in blood pressure cannot be excluded altogether, since there are few data on the hemodynamic responses during longterm low-dose ANP infusion. Small resistance arterioles, however, have recently been shown to be unresponsive to ANP, 29 and this may explain in part the lack of increased mesenteric blood flow found after infusion of ANP. 28 Results from different laboratories thus suggest a complex mechanism for the hemodynamic effect of ANP, including dilatation of larger arterial vessels, venodilatation, decreased cardiac output, or decreased blood volume.…”

Section: Discussionmentioning

confidence: 99%

Decreased density of vascular receptors for atrial natriuretic peptide in DOCA-salt hypertensive rats.

Schiffrin¹,

St‐Louis²

1987

Hypertension

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SUMMARY We have previously found that vascular receptors for atrial natriuretic peptide (ANP) in the rat are down-regulated by volume expansion. For this reason vascular ANP receptor density and affinity were examined in a model of volume-expanded hypertension, the deoxycorticosterone acetate (DOCA)-salt hypertensive rat. The density of mesenteric vascular ANP binding sites was decreased in DOCA-salt hypertensive rats from a control value in uninephrectomized rats of 203 ± 25 fmol/mg protein to 60 ± 13 fmol/mg protein (p<0.01). The sensitivity of norepinephrine-precontracted aorta to ANP was significantly reduced in DOCA-salt hypertensive rats (p<0.001). DOCA-salt hypertensive rats infused intravenously for 4 days with ANP, 100 to 300 ng/hr, did not experience a lowering of blood pressure, in contrast to the significant reduction in blood pressure seen in twokidney, one clip Goldblatt hypertensive rats similarly infused. In the latter there was no natriuretic response to ANP, while in the DOCA-salt hypertensive rats natriuresis occurred without lowering of blood pressure. In the DOCA-salt hypertensive rats plasma ANP concentration was increased to 68 ± 8 fmol/ml from 10 ± 1 fmol/ml in uninephrectomized rats. In conclusion, raised ANP concentration in plasma of volume-expanded hypertensive rats (DOCA-salt hypertension) may result in decreased density of ANP vascular receptors. These results suggest that a decrement in the number of ANP receptors may be a cause of decreased sensitivity of vascular responses to ANP in vitro and resistance to the blood pressure-lowering action of ANP in vivo. (Hypertension 9: 504-512, 1987 Received May 6, 1986; accepted December 3, 1986. of the rat. 8 We have recently shown that these ANP binding sites are down-regulated after sodium-loading uninephrectomized rats and in one-kidney, one clip (1K1C) Goldblatt hypertensive rats, 9 a model of nonrenin-dependent, volume-expanded hypertension. After mineralocorticoid administration we have also found a decrement in the density of vascular ANP receptors.10 In all these experimental models sensitivity to ANP of norepinephrine (NE)-precontracted aortic strips was decreased. Infusion of ANP lowers the blood pressure of spontaneously hypertensive rats," a genetic model of hypertension, and of two-kidney, one clip (2K1C) Goldblatt hypertensive rats, 12 a renin-dependent, non-volume-expanded form of experimental hypertension. In contrast, 1K1C Goldblatt hypertensive rats are relatively resistant to the hypotensive action of ANP. 13 In 1K1C hypertensive rats, vascular ANP sites are decreased in density, 9 while in the 2K1C model no down-regulation of vascular binding sites is present. 9 We therefore hypothesized that in another experimental model of volume-expanded hypertension, the deoxycorticosterone acetate (DOCA)-salt 504 Downloaded from http://ahajournals.org by on April 28, 2019

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“…In contrast, the relevance of the direct vasodilating ANP effect is controversial, because very variable GC-A levels are expressed in different vascular beds. 68,73 To characterize this issue, in a recent study, we selectively deleted GC-A in vascular smooth muscle cells (SMC GC-A KO) using Cre-lox technology. 74 Surprisingly, in spite of the clear abolition of the direct vasorelaxing effects of ANP, the resting arterial blood pressure of conscious SMC GC-A KO mice was completely normal ( Figure 3A).…”

Section: Endocrine Actions Of the Anp/gc-a System Cooperate In Acute mentioning

confidence: 99%

Structure, Regulation, and Function of Mammalian Membrane Guanylyl Cyclase Receptors, With a Focus on Guanylyl Cyclase-A

Kühn

2003

Circulation Research

239

161

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Abstract-Besides soluble guanylyl cyclase (GC), the receptor for NO, there are at least seven plasma membrane enzymes that synthesize the second-messenger cGMP. All membrane GCs (GC-A through GC-G) share a basic topology, which consists of an extracellular ligand binding domain, a short transmembrane region, and an intracellular domain that contains the catalytic (GC) region. Although the presence of the extracellular domain suggests that all these enzymes function as receptors, specific ligands have been identified for only three of them (GC-A through GC-C). GC-A mediates the endocrine effects of atrial and B-type natriuretic peptides regulating arterial blood pressure and volume homeostasis and also local antihypertrophic actions in the heart. GC-B is a specific receptor for C-type natriuretic peptide, having more of a paracrine function in vascular regeneration and endochondral ossification. GC-C mediates the effects of guanylin and uroguanylin on intestinal electrolyte and water transport and on epithelial cell growth and differentiation. GC-E and GC-F are colocalized within the same photoreceptor cells of the retina and have an important role in phototransduction. Finally, the functions of GC-D (located in the olfactory neuroepithelium) and GC-G (expressed in highest amounts in lung, intestine, and skeletal muscle) are completely unknown. This review discusses the structure and functions of membrane GCs, with special emphasis on the physiological endocrine and cardiac functions of GC-A, the regulation of hormone-dependent GC-A activity, and the relevance of alterations of the atrial natriuretic peptide/GC-A system to cardiovascular diseases. (Circ Res. 2003;93:700-709.)

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Synthetic atrial natriuretic factor does not dilate resistance-sized arteries.

Cited by 43 publications

References 6 publications

Low-dose infusion of atrial natriuretic factor in mild essential hypertension.

Low-dose infusion of atrial natriuretic factor in mild essential hypertension.

Decreased density of vascular receptors for atrial natriuretic peptide in DOCA-salt hypertensive rats.

Structure, Regulation, and Function of Mammalian Membrane Guanylyl Cyclase Receptors, With a Focus on Guanylyl Cyclase-A

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