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Trinity J Bivalacqua

Publications and source records attributed to Trinity J Bivalacqua.

44 records · Page 3Linked to original sources
PubMed2002

Adenoviral gene transfer of endothelial nitric-oxide synthase (eNOS) partially restores normal pulmonary arterial pressure in eNOS-deficient mice.

It has been shown that mice deficient in the gene coding for endothelial nitric-oxide synthase (eNOS) have increased pulmonary arterial pressure and pulmonary vascular resistance. In the present study, the effect of transfer to the lung of an adenoviral vector encoding the eNOS gene (AdCMVeNOS) on pulmonary arterial pressure and pulmonary vascular resistance was investigated in eNOS-deficient mice. One day after intratracheal administration of AdCMVeNOS to eNOS(-/-) mice, there was an increase in eNOS protein, cGMP levels, and calcium-dependent conversion of l-arginine to l-citrulline in the lung. The increase in eNOS protein and activity in eNOS(-/-) mice was associated with a reduction in mean pulmonary arterial pressure and pulmonary vascular resistance when compared with values in eNOS-deficient mice treated with vehicle or a control adenoviral vector coding for beta-galactosidase, AdCMVbetagal. These data suggest that in vivo gene transfer of eNOS to the lung in eNOS(-/-) mice can increase eNOS staining, eNOS protein, calcium-dependent NOS activity, and cGMP levels and partially restore pulmonary arterial pressure and pulmonary vascular resistance to near levels measured in eNOS(+/+) mice. Thus, the major finding in this study is that in vivo gene transfer of eNOS to the lung in large part corrects a genetic deficiency resulting from eNOS deletion and may be a useful therapeutic intervention for the treatment of pulmonary hypertensive disorders in which eNOS activity is reduced.

Adenoviridae↗
PubMed2002

A comparison of the NADPH oxidase in human sperm and white blood cells.

The mechanism of reactive oxygen species (ROS) generation in human sperm has recently been found to depend upon a novel NADPH-oxidase (NOX5) resembling the multicomponent NADPH-oxidase of white blood cells (WBCs). The purpose of our study was to compare the ROS producing activity of NOX5 in sperm and NADPH-oxidase of WBCs, and to investigate the role of protein kinase C (PKC) in NOX5 activation. A combination of electron paramagnetic resonance (EPR), chemiluminescence (CL), and nitroblue tetrazolium (NBT) dye reduction were used to monitor ROS production by sperm. The involvement of PKC in NOX5 activation was investigated using myristate acetate (PMA), and the PKC inhibitor GF-109203X. The presence of b cytochrome in NOX5 was investigated by spectrophotometry. PMA-stimulated WBCs produced superoxide dismutase -- inhibitable EPR signals for both superoxide and hydroxyl radicals. Sperm did not produce these spectra with or without PMA stimulation. WBCs generated significantly increased levels of CL and reduced NBT after PMA stimulation; whereas sperm did not increase the CL response or reduce NBT. Adenosine triphosphate (ATP) levels in WBCs were significantly reduced after PMA stimulation, whereas sperm ATP levels did not change. The characteristic spectra of b cytochrome observed after dithionite reduction of WBCs was not observed with sperm under similar conditions. These results indicate that the ROS producing activity of NOX5 is significantly lower than the WBC NADPH-oxidase, and suggest that the activation mechanism of NOX5 in sperm is independent of PKC.

Adenosine Triphosphate↗
PubMed2002

Role of nitric oxide in mediating vasodilator responses to opioid peptides in the rat.

1. Endomorphins 1 and 2, endogenous ligands for the mu-opioid receptor, and nociceptin (orphanin FQ; OFQ), an endogenous ligand for the ORL1 receptor, have vasodilator activity in the vascular bed of the hindquarters of the rat. In the present study, the role of nitric oxide (NO), vasodilator prostaglandins and the opening of KATP channels in mediating vasodilator responses to these novel agonists was investigated in the rat. 2. Under constant-flow conditions, injections of endomorphins 1 and 2, PL017 ([N-MePhe3,D-Pro4]-morphiceptin), nociceptin and Tyr-D-Ala-Gly-MePhe-Gly(ol)-enkephalin (DAMGO) produced dose-dependent decreases in hindquarters perfusion pressure. Vasodilator responses to endomorphin 1 and 2, acetylcholine and adrenomedullin, were attenuated by the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) at a time when vasodilator responses to nociceptin, adrenomedullin and the NO donor diethylamine/NO were not altered. 3. Vasodilator responses to endomorphins 1 and 2, nociceptin, PL017 and DAMGO were not altered after administration of sodium meclofenamate at a time when vasodilator responses to arachidonic acid were reduced significantly or after administration of U-37883A at a time when vasodilator responses to levcromakalim were reduced significantly. 4. The results of these studies indicate that vasodilator responses to endomorphins 1 and 2, PL017 and DAMGO are mediated, in large part, by the release of NO, whereas vasodilator responses to nociceptin are mediated by an L-NAME-insensitive mechanism. Moreover, these results demonstrate that the vasodilator responses to these peptides are not due to the release of vasodilator prostaglandins or the opening of KATP channels in the hindquarters vascular bed of the rat.

Animals↗
PubMed2002

Vasodilator responses to adenosine and hyperemia are mediated by A(1) and A(2) receptors in the cat vascular bed.

Hemodynamic responses to adenosine, the A(1) receptor agonists N(6)-cyclopentyladenosine (CPA) and adenosine amine congener (ADAC), and the A(2) receptor agonist 5'-(N-cyclopropyl)-carboxamido-adenosine (CPCA) were investigated in the hindquarter vascular bed of the cat under constant-flow conditions. Injections of adenosine, CPA, ADAC, CPCA, ATP, and adenosine 5'-O-(3-thiotriphosphate) (ATPgamma S) into the perfusion circuit induced dose-related decreases in perfusion pressure. Vasodilator responses to the A(1) agonists were reduced by the A(1) receptor antagonists KW-3902 and CGS-15943, whereas responses to CPCA were reduced by the A(2) antagonist KF-17837. Vasodilator responses to adenosine were reduced by KW-3902, CGS-15943, and by KF-17837, suggesting a role for both A(1) and A(2) receptors. Vasodilator responses to ATP and the nonhydrolyzable ATP analog ATP gamma S were not attenuated by CGS-15943 or KF-17837. After treatment with the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester, the cyclooxygenase inhibitor sodium meclofenamate, or the ATP-dependent K(+) (K) channel antagonists U-37883A or glibenclamide, responses to adenosine and ATP were not altered. Responses to adenosine, CPA, and CPCA were increased in duration by rolipram, a type 4 cAMP phosphodiesterase inhibitor, but were not altered by zaprinast, a type 5 cGMP phosphodiesterase inhibitor. When blood flow was interrupted for a 30-s period, the magnitude and duration of the reactive vasodilator response were reduced by A(1) and A(2) receptor antagonists. These data suggest that vasodilator responses to adenosine and the A(1) and A(2) agonists studied are not dependent on the release of cyclooxygenase products, nitric oxide, or the opening of K channels in the regional vascular bed of the cat. The present data suggest a role for cAMP in mediating responses to adenosine and suggest that vasodilator responses to adenosine and to reactive hyperemia are mediated in part by A(1) and A(2) receptors in the hindquarter vascular bed of the cat.

Adenosine↗
PubMed2002

Comparative responses to alpha,beta-methylene-ATP in cat pulmonary, mesenteric, and hindquarter vascular beds.

Responses to the P2X-purinoceptor agonist alpha,beta-methylene-ATP (alpha,beta-MeATP) were investigated in the pulmonary, hindquarter, and mesenteric vascular beds in the cat. Under constant-flow conditions, injections of alpha,beta-MeATP caused dose-related increases in perfusion pressure in the pulmonary and hindquarter beds and a biphasic response in the mesenteric circulation. In the pulmonary vascular bed, the order of potency was alpha,beta-MeATP > U-46619 > angiotensin II, whereas, in the hindquarters, the order of potency was angiotensin II > U-46619 > alpha,beta-MeATP. The order of potency was similar in the hindquarter and mesenteric beds when the pressor component of the response to alpha,beta-MeATP was compared with responses to angiotensin II and U-46619. The P2X-receptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid attenuated the pressor response to alpha,beta-MeATP in the hindquarter circulation and the pressor component in the mesenteric vascular bed. Pressor responses to alpha,beta-MeATP were not altered by cyclooxygenase, alpha-adrenergic, or angiotensin AT(1) antagonists. These data show that alpha,beta-MeATP has potent pressor activity in the pulmonary circulation, where it was 100-fold more potent than angiotensin II. In contrast, alpha,beta-MeATP had modest pressor activity in the systemic bed, where it was 1,000-fold less potent than angiotensin II. These data suggest that responses to alpha,beta-MeATP are dependent on the vascular bed studied and may be dependent on the density of P2X receptors in the vascular bed.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMedDate not supplied

Localization of peripheral dopamine D1 and D2 receptors in rat and human seminal vesicles.

Dopamine, an established neurotransmitter in the central nervous system, is recognized for its role in penile erection and ejaculation in rats. However, its complete mechanism of action in the genitourinary tract is unknown. The objective of this study was to investigate the existence and expression of peripheral dopamine D1 and D2 receptor messenger RNAs (mRNAs) and corresponding proteins in rat and human seminal vesicles. The seminal vesicle tissues of male Sprague-Dawley rats and human radical prostatectomy specimens were used to extract total RNA and proteins, and to prepare slide sections. Rat hypothalamus tissue served as a control for dopamine D1 and D2 receptors. Testing for the presence and expression of peripheral dopamine D1 and D2 receptor mRNAs in rat and human seminal vesicle tissues was performed by reverse transcription-polymerase chain reaction. Western blotting was used to detect corresponding proteins of D1 and D2 receptors. Immunohistochemical staining using rabbit antipeptide polyclonal antibodies was employed to identify and anatomically localize dopamine D1 and D2 receptor proteins in rat and human seminal vesicles. Dopamine D1 and D2 receptor transcripts were detected in both human and rat seminal vesicle tissues. Western blot analysis demonstrated that peripheral dopamine D1 and D2 receptor proteins exist in both human and rat seminal vesicle tissues. Immunohistochemical analysis demonstrated the localization of peripheral dopamine D1 and D2 receptors to the smooth muscle layer of human and rat seminal vesicles. The results of this study demonstrate that peripheral dopamine D1 and D2 receptors are present in the seminal vesicle tissue in both rats and humans. Although these results suggest that seminal emission may be mediated in part by the stimulation of peripheral dopamine receptors located in the seminal vesicles, the functional significance of dopamine in male reproductive tract has yet to be fully defined.

Animals↗
PubMedDate not supplied

Cavernous neurotomy causes hypoxia and fibrosis in rat corpus cavernosum.

The etiologies of erectile dysfunction (ED) after nerve-sparing radical prostatectomy have not been clearly elucidated. The aim of this study was to evaluate the effects of cavernous nerve injury on cavernous fibrosis, and to consider measures to prevent irreversible damage to the cavernous tissues. Twenty male Sprague-Dawley rats constituted the study population. The animals were divided into 2 groups; group 1 consisted of sham-operated rats (n = 10), and group 2 consisted of rats that underwent incision of both cavernous nerves (n = 10). Three months later, all rats underwent intracavernous papaverine injection (300 and 600 mg), and intracorporal pressures were recorded. Transforming growth factor-beta(1) (TGF-beta(1)) messenger RNA (mRNA) expression from rat penile tissue was measured using reverse transcriptase-polymerase chain reaction. Hypoxia-inducible factor-1alpha (HIF-1alpha), TGF-beta(1), and collagen I and III protein expressions were determined by Western blot analysis and immunohistochemical staining. Erectile function as studied with intracavernosal papaverine injection and histological analysis of penile cross-sections at 3 months was similar in both groups. TGF-beta(1) mRNA expression, HIF-1alpha, TGF-beta(1), and collagen I and III protein expressions were significantly greater in the neurotomy group. Immunohistochemical staining for TGF-beta(1), HIF-1alpha, and collagen III were qualitatively more positive in the neurotomy group, whereas collagen I staining was similar. This study demonstrates an increase in TGF-beta(1), HIF-1alpha, and collagen III synthesis in rat cavernosal smooth musculature after cavernous neurotomies. In theory, cavernous fibrosis may be reduced by employing various vasoactive agents or interventions that increase oxygenation to the corporal tissues during the postoperative period.

Animals↗