This study reports the cardiovascular and renal actions of a novel and newly synthesized 27-amino acid peptide termed vasonatrin peptide (VNP). VNP is a chimera of atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP). This synthetic peptide possesses the 22-amino acid structure of CNP, which is a cardiovascular selective peptide of endothelial origin and is structurally related to ANP. VNP also possesses the five-amino acid COOH terminus of ANP. The current study demonstrates both in vitro and in vivo that VNP possesses the venodilating actions of CNP, the natriuretic actions of ANP, and unique arterial vasodilating actions not associated with either ANP or CNP. (J. Clin. Invest. 1993. 92:2048-2052
C-type natriuretic peptide (CNP) is an endothelium-derived peptide that shares structural homology with atrial natriuretic peptide (ANP). CNP causes greater endothelium-independent relaxations in veins compared with arteries. Relaxations to CNP in porcine coronary arteries are mediated by hyperpolarization of the smooth muscle membrane. Experiments were designed to investigate the mechanism(s) by which CNP causes relaxation in canine femoral veins. Rings of canine femoral veins without endothelium were suspended for measurement of isometric force in organ chambers. Concentration-response curves to CNP were obtained in veins contracted with either endothelin-1 (10(-8) M), KCl (40 mM), phenylephrine (10(-6) M) or prostaglandin F2 alpha (2 x 10(-6) M) in the absence and presence of BQ-123 (10(-6) M), NG-monomenthyl-L-arginine (L-NMMA; 10(-4) M), HS-142-1 (10(-5) M), methylene blue (10(-5) M), or potassium channel blockers, tetraethylammonium chloride (TEA; 10(-3) M), charybdotoxin (10(-7) M), glibenclamide (10(-7) M), or apamin (10(-7) M). Relaxations to CNP were significantly attenuated when the tissue was contracted with KCl and endothelin-1. During contraction to either phenylephrine or prostaglandin F2 alpha, relaxations to CNP were inhibited by HS-142-1, methylene blue, TEA, and charybdotoxin, but not by L-NMMA, glibenclamide, or apamin. In separate experiments, guanosine 3',5'-cyclic monophosphate increased twofold within 10-60 s after the addition of CNP (10(-8) M). These data suggest that CNP mediates relaxation of canine femoral veins through activation of large-conduction, calcium-activated potassium channels and activation of particulate and soluble guanylate cyclase.
The present study determined circulating concentrations of atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) in Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) and also investigated the vasorelaxing action of ANP and CNP on isolated contracted aorta. We also defined the vasorelaxing action of a novel and newly synthesized 27-amino acid chimera of ANP and CNP termed vasonatrin peptide (VNP), which we compared with ANP and CNP in WKY rats and SHR. Plasma and urinary cyclic GMP and sodium excretion were also investigated. Plasma ANP was increased in SHR in contrast to no change in circulating CNP. Plasma and urinary cyclic GMP and sodium excretion were no different between WKY rats and SHR. In WKY rats maximal relaxations to VNP in aortic rings without endothelium were greater than those to ANP and CNP. In SHR aortic rings the potency of VNP relaxation was preserved, the actions of ANP were enhanced, and the actions of A trial natriuretic peptide (ANP) is a potent natri-/ \ uretic and vasoactive peptide that is produced -Z X . by atrial myocytes and is important in the control of cardiorenal homeostasis.13 ANP binds to a specific participate guanylyl cyclase receptor termed natriuretic peptide receptor-A (NPR-A), 4 which is expressed in endothelial and in renal epithelial cells 5 and mediates its biological actions. Previous reports have demonstrated that the vasoactive and natriuretic actions of ANP require its COOH terminus. 6 C-type natriuretic peptide (CNP) is a newly identified 22-amino acid peptide that like ANP has a 17-amino acid ring formed by a disulfide bond. Unlike ANP, CNP lacks the COOH terminus amino acid. CNP is genetically distinct from ANP 7 and functions biologically via a separate paniculate guanylyl cyclase receptor, natriuretic peptide receptor-B (NPR-B), 4 which is expressed in vascular smooth muscle cells and in the kidney. While ANP and CNP both decrease cardiac preload and arterial pressure, ANP-mediated decreases in arterial pressure are in part secondary to increases in sodium excretion, which is minimal with CNP. 910 In contrast, CNP is a potent endothelium-independent venodilator CNP were markedly impaired. In association with these vasorelaxing actions, these data suggest that (1) circulating CNP is not different in SHR and WKY rats, but the aortic relaxing action of CNP is markedly impaired in SHR; (2) endogenous plasma ANP is significantly increased in SHR without associated increases in plasma or urinary cyclic GMP; (3) there is an increase in aortic relaxation to exogenous ANP in SHR; and (4) VNP has a potent endothelium-independent aortic relaxing action in both WKY rats and SHR. These data suggest differential regulation of ANP and CNP and their vascular actions in SHR. These data also suggest that VNP could have an important therapeutic role in hypertension. and ANP is not.11 Both CNP and ANP possess arterial vasorelaxing actions.12 Furthermore, ANP is of cardiac origin and functions as a circulating hormone, whereas CNP is synthes...
CNP functions as a coronary vasodilator through activation of cGMP by way of particulate guanylate cyclase. CNP-mediated coronary vasodilation is attenuated by intracoronary HS-142-1. Intracoronary HS-142-1 does not affect acetylcholine-mediated coronary vasodilation. These observations support a role for exogenous CNP as a potent coronary vasodilator.
Ovarian metastasis from early-stage squamous cervical cancer is rare. We report a case of unilateral ovarian metastasis from squamous cervical cancer IA1. Although ovarian metastasis from early-stage squamous cervical cancer is rare, gynecological oncologists should not overlook its possibility.
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