Showing papers by "Hunter C. Champion published in 2000"
TL;DR: Erectile function is significantly lower in the TGF-beta1-injected and surgical-injury rats after 6 weeks at a time when iNOS is upregulated and constitutive NOS is downregulated, suggesting that iNos may alter the vascular tone in the penis.
111 citations
TL;DR: The past 20 years of research on erectile physiology have increased understanding of the biochemical factors and intracellular mechanisms responsible for corpus cavernosal smooth muscle contraction and relaxation, and revealed that ED is predominantly a disease of vascular origin.
101 citations
TL;DR: In vivo C GRP lung gene transfer attenuates the increase in PVR and RVM, pulmonary vascular remodeling, and pressor responses in chronically hypoxic mice, suggesting that CGRP gene transfer alone and with a cAMP phosphodiesterase inhibitor may be useful for the treatment of pulmonary hypertensive disorders.
Abstract: Background—Calcitonin gene–related peptide (CGRP) is believed to play an important role in maintaining low pulmonary vascular resistance (PVR) and in modulating pulmonary vascular responses to chronic hypoxia; however, the effects of adenovirally mediated gene transfer of CGRP on the response to hypoxia are unknown. Methods and Results—In the present study, an adenoviral vector encoding prepro-CGRP (AdRSVCGRP) was used to examine the effects of in vivo gene transfer of CGRP on increases in PVR, right ventricular mass (RVM), and pulmonary vascular remodeling that occur in chronic hypoxia in the mouse. Intratracheal administration of AdRSVCGRP, followed by 16 days of chronic hypoxia (Fio2 0.10), increased lung CGRP and cAMP levels. The increase in pulmonary arterial pressure (PAP), PVR, RVM, and pulmonary vascular remodeling in response to chronic hypoxia was attenuated in animals overexpressing prepro-CGRP, whereas systemic pressure was not altered while in chronically hypoxic mice, angiotensin II and endo...
101 citations
TL;DR: Enhanced expression of eNOS employing an adenoviral vector significantly increased the erectile response to cavernosal nerve stimulation in the aged rat, similar to the response observed in younger rats.
Abstract: Nitric oxide (NO) is the principal mediator of penile erection. NO is synthesized by a variety of nitric oxide synthases (NOS). It has been demonstrated that a decrease in NOS activity, as observed in aging, is associated with a diminished erectile response. The objective of this study was to determine if adenoviral-mediated gene transfer of eNOS could reverse age-related erectile dysfunction in the rat. Two groups of animals were transfected with adenoviruses: (1) aged rats (60 weeks) with AdRSVbetagal; and (2) aged rats (60 weeks) with AdRSVeNOS. Five days after transfection, these study animals underwent cavernosal nerve stimulation (CNS) to assess erectile function and their responses were compared with young (20 weeks) control rats. Cross-sections of the rat penises transfected with AdRSVeNOS were examined after trichrome staining. Adenoviral transduction efficiency of beta-galactosidase reporter gene was measured by a galacto-light chemiluminescent reporter gene assay in cavernosal tissues of rats administered AdRSVbetagal. The transgene expression of eNOS was examined by RT-PCR in rats transfected with AdRSVbetagal and AdRSVeNOS. eNOS and iNOS protein levels were measured by Western blot analysis, and cGMP levels were assessed in cavernosal tissue by enzyme immunoassay. Adenoviral expression of the beta-galactosidase reporter gene was observed in cavernosal tissue for up to 30 days, with peak expression registered at 5 days after intracavernosal administration of AdRSVbetagal. Cross-sections of the rat penises transfected with the AdRSVeNOS revealed no pathological (morphological or histological) changes. Five days after administration of AdRSVeNOS, eNOS protein, mRNA and cGMP levels in the corpora cavernosa were significantly increased (P 0.05). In conclusion, enhanced expression of eNOS employing an adenoviral vector significantly increased the erectile response to cavernosal nerve stimulation in the aged rat, similar to the response observed in younger rats. These data suggest that in vivo adenoviral gene transfer of eNOS can physiologically improve erectile function in the aged rat.
91 citations
TL;DR: Findings indicate that ADM stimulates cell proliferation in the rat ZG, through CGRP-(8-37)- and ADM-(22-52)-sensitive receptors, and the mitogenic effect of ADM is mediated by activation of the TK-MAPK cascade, without any involvement of the adenylate cyclase/protein kinase A-, phospholipase C/ protein kinase C-, and COX- or lipoxygenase-dependent signaling pathways.
Abstract: The effect of adrenomedullin (ADM) on the proliferative activity of the rat adrenal cortex has been investigated in vivo, using an in situ perfusion technique of the intact left gland. ADM and other chemicals were dissolved in the perfusion medium, and the perfusion was continued for 180 min. ADM infusion concentration dependently increased the mitotic index and [3H]thymidine incorporation into DNA in the zona glomerulosa (ZG; the maximal effective concentration was 10−8 m), but not in inner adrenocortical layers, where basal proliferative activity was negligible. The effect of 10−8 m ADM was equipotently counteracted by both the calcitonin gene-related peptide (CGRP) type 1 receptor antagonist CGRP-(8–37) and ADM-(22–52). The adenylate cyclase inhibitor SQ-22536 (10−4 m), the cAMP blocker Rp-cAMP-S (10−3 m), and the protein kinase A inhibitor H-89 (10−5 m), although counteracting the ZG proliferogenic action of 10−9 m ACTH, did not affect the 10−8 m ADM-elicited increase in ZG DNA synthesis. Similar resu...
54 citations
TL;DR: The data suggest that ET‐1[1–31] is a selective agonist of the ETA‐receptor subtype, and enhances proliferation of cultured rat ZG cells through the PKC‐ and TK‐dependent activation of p42/p44 MAPK cascade.
40 citations
TL;DR: This is the first report of a right-heart catheterization technique to measure pulmonary vascular pressures and responses in the intact-chest, spontaneously breathing mouse and should prove useful for the investigation of pulmonary vascular responses in transgenic mice.
Abstract: The present study employed a new right-heart catheterization technique to measure pulmonary arterial pressure, pulmonary arterial wedge pressure, and pulmonary vascular resistance in anesthetized i...
34 citations
TL;DR: It is demonstrated that the endomorphins relax aortic vascular smooth muscle from the rat aorta by an endothelium-dependant mechanism.
18 citations
TL;DR: The data suggest that the nonpeptide angiotensin analog L-163,491 has partial agonist activity, which is dependent on the stimulation of ang Elliotensin AT(1) receptors in the hindquarters vascular bed of the cat.
13 citations
TL;DR: The occasional use of over-the-counter (OTC) epinephrine inhalers appears to be safe and effective when used according to labeled instruction by individuals with mild, intermittent asthma as discussed by the authors.
11 citations
TL;DR: The results of the present study demonstrate that galantide, a putative antagonist for the galanin receptor, has more potent agonist activity than Galanin in increasing intracavernosal pressure in the cat, and suggest that galan in causes penile erection by an NO/cGMP-dependent mechanism.
TL;DR: The effects of the purinergic agonists, ATP, ATPγS, UTP, and 2-Met-Thio AP, were investigated in the hindlimb vascular bed of the cat under constant-flow conditions.
Abstract: The effects of the purinergic agonists, ATP, ATPγS, UTP, and 2-Met-Thio AP, were investigated in the hindlimb vascular bed of the cat. Under constant-flow conditions, injections of the purinergic a...
01 Jan 2000
TL;DR: NOS types I, II, and III are found in the skeletal muscle vascular bed, with types I and III being found under physiological conditions, and the mRNA for type II NOS being up-regulated under pathophysiological conditions, such as in gram-negative sepsis.
Abstract: Nitric oxide (NO) is a free radical synthesized by NO synthase (NOS), an enzyme that exists in three identified isoforms in the body (Kerwin et al 1995) The isoforms of NOS have been named on the basis of location: neural constitutive NOS (type I or nNOS), inducible NOS (type II or iNOS), and endothelial constitutive NOS (type III or eNOS) (Kerwin et al 1995) Although all forms are distinct based on their location, each form uses L-arginine in the formation of NO in a reaction that requires molecular oxygen and NADPH as cosubstrates with L-citrulline produced as a by-product of the reaction NOS types I, II, and III are found in the skeletal muscle vascular bed, with types I and III being found under physiological conditions, and the mRNA for type II NOS being up-regulated under pathophysiological conditions, such as in gram-negative sepsis (Kerwin et al 1995; Reid 1998)