Patients' and Clinicians' Experiences with In-person, Video, and Phone Modalities for Opioid Use Disorder Treatment: A Qualitative Study.

BACKGROUND: Opioid use disorder (OUD) is a chronic condition that requires regular visits and care continuity. Telehealth implementation has created multiple visit modalities for OUD care. There is limited knowledge of patients' and clinicians' perceptions and experiences related to multi-modality care and when different modalities might be best employed. OBJECTIVE: To identify patients' and clinicians' experiences with multiple visit modalities for OUD treatment in primary care. DESIGN: Comparative case study, using video- and telephone-based semi-structured interviews. PARTICIPANTS: Patients being treated for OUD (n = 19) and clinicians who provided OUD care (n = 15) from two primary care clinics within the same healthcare system. APPROACH: Using an inductive approach, interviews were analyzed to identify patients' and clinicians' experiences with receiving/delivering OUD care via different visit modalities. Clinicians' and patients' experiences were compared using a group analytical process. KEY RESULTS: Patients and clinicians valued having multiple modalities available for care, with flexibility identified as a key benefit. Patients highlighted the decreased burden of travel and less social anxiety with telehealth visits. Similarly, clinicians reported that telehealth decreased medical intrusion into the lives of patients stable in recovery. Patients and clinicians saw the value of in-person visits when establishing care and for patients needing additional support. In-person visits allowed the ability to conduct urine drug testing, and to foster relationships and trust building, which were more difficult, but not impossible via a telehealth visit. Patients preferred telephone over video visits, as these were more private and more convenient. Clinicians identified benefits of video, including being able to both hear and see the patient, but often deferred to patient preference. CONCLUSIONS: Considerations for utilization of visit modalities for OUD care were identified based on patients' needs and preferences, which often changed over the course of treatment. Continued research is needed determine how visit modalities impact patient outcomes.

Impact of Blood Rheology on Transition to Turbulence and Wall Vibration Downstream of a Stenosis.

Previous experimental flow studies have demonstrated a delay (∼20%) in transition to turbulence for whole blood compared to a Newtonian analog fluid in both a straight pipe and eccentric stenosis model with ridged walls. The impact of wall compliance on the transition to turbulence of blood compared to Newtonian analog and on wall vibration is unknown. The present study employed flexible walls downstream of an eccentric stenosis model and examined the wall vibration during the transition to turbulence with whole blood and a Newtonian analog. Measurements of tube wall vibration velocity (WVV) were used as an indicator of the turbulence level within the flexible tube. WVV was measured at 5, 10, and 15 diameters downstream of the stenosis using a laser Doppler vibrometer at Reynolds numbers 0, 200, 300, 350, 400, 450, 500, 550, 600, 650, 700, and 750. The root mean squares (RMS) of the measured WVV were utilized as an indirect measure of fluid velocity fluctuations present at that location, and hence, an indicator of transition to turbulence. WVV RMS was near-constant until approximately Reynolds number 400. It increased monotonically with Reynolds number for both whole blood and the Newtonian fluid. No differences in the transition to turbulence were observed between whole blood and the Newtonian fluid, as the WVV RMS curves were remarkably similar in shape. This result suggests that rheology had minimal impact on the WVV downstream of a stenosis for transition to turbulence since the fluids had a similar level of vibration.

Transition to Turbulence Downstream of a Stenosis for Whole Blood and a Newtonian Analog Under Steady Flow Conditions.

Blood, a multiphase fluid comprised of plasma, blood cells, and platelets, is known to exhibit a shear-thinning behavior at low shear rates and near-Newtonian behavior at higher shear rates. However, less is known about the impact of its multiphase nature on the transition to turbulence. In this study, we experimentally determined the critical Reynolds number at which the flow began to transition to turbulence downstream of eccentric stenosis for whole porcine blood and a Newtonian blood analog (water-glycerin mixture). Velocity profiles for both fluids were measured under steady-state flow conditions using an ultrasound Doppler probe placed 12 diameters downstream of eccentric stenosis. Velocity was recorded at 21 locations along the diameter at 11 different flow rates. Normalized turbulent kinetic energy was used to determine the critical Reynolds number for each fluid. Blood rheology was measured before and after each experiment. Tests were conducted on five samples of each fluid inside a temperature-controlled in vitro flow system. The viscosity at a shear rate of 1000 s-1 was used to define the Reynolds number for each fluid. The mean critical Reynolds numbers for blood and water-glycerin were 470 ± 27.5 and 395 ± 10, respectively, indicating a ∼19% delay in transition to turbulence for whole blood compared to the Newtonian fluid. This finding is consistent with a previous report for steady flow in a straight pipe, suggesting some aspect of blood rheology may serve to suppress, or at least delay, the onset of turbulence in vivo.

COVID-19 Mortality Among American Indian and Alaska Native Persons - 14 States, January-June 2020.

American Indian/Alaska Native (AI/AN) persons experienced disproportionate mortality during the 2009 influenza A(H1N1) pandemic (1,2). Concerns of a similar trend during the coronavirus disease 2019 (COVID-19) pandemic led to the formation of a workgroup* to assess the prevalence of COVID-19 deaths in the AI/AN population. As of December 2, 2020, CDC has reported 2,689 COVID-19-associated deaths among non-Hispanic AI/AN persons in the United States.† A recent analysis found that the cumulative incidence of laboratory-confirmed COVID-19 cases among AI/AN persons was 3.5 times that among White persons (3). Among 14 participating states, the age-adjusted AI/AN COVID-19 mortality rate (55.8 deaths per 100,000; 95% confidence interval [CI] = 52.5-59.3) was 1.8 (95% CI = 1.7-2.0) times that among White persons (30.3 deaths per 100,000; 95% CI = 29.9-30.7). Although COVID-19 mortality rates increased with age among both AI/AN and White persons, the disparity was largest among those aged 20-49 years. Among persons aged 20-29 years, 30-39 years, and 40-49 years, the COVID-19 mortality rates among AI/AN were 10.5, 11.6, and 8.2 times, respectively, those among White persons. Evidence that AI/AN communities might be at increased risk for COVID-19 illness and death demonstrates the importance of documenting and understanding the reasons for these disparities while developing collaborative approaches with federal, state, municipal, and tribal agencies to minimize the impact of COVID-19 on AI/AN communities. Together, public health partners can plan for medical countermeasures and prevention activities for AI/AN communities.

Characterization of Transition to Turbulence for Blood in a Straight Pipe Under Steady Flow Conditions.

Blood is a complex fluid that, among other things, has been established to behave as a shear thinning, non-Newtonian fluid when exposed to low shear rates (SR). Many hemodynamic investigations use a Newtonian fluid to represent blood when the flow field of study has relatively high SR (>200 s-1). Shear thinning fluids have been shown to exhibit differences in transition to turbulence (TT) compared to that of Newtonian fluids. Incorrect prediction of the transition point in a simulation could result in erroneous hemodynamic force predictions. The goal of the present study was to compare velocity profiles near TT of whole blood and Newtonian blood analogs in a straight rigid pipe with a diameter 6.35 mm under steady flow conditions. Rheology was measured for six samples of whole porcine blood and three samples of a Newtonian fluid, and the results show blood acts as a shear thinning non-Newtonian fluid. Measurements also revealed that blood viscosity at SR = 200 s-1 is significantly larger than at SR = 1000 s-1 (13.8%, p < 0.001). Doppler ultrasound (DUS) was used to measure velocity profiles for blood and Newtonian samples at different flow rates to produce Reynolds numbers (Re) ranging from 1000 to 3300 (based on viscosity at SR = 1000 s-1). Two mathematically defined methods, based on the velocity profile shape change and turbulent kinetic energy (TKE), were used to detect TT. Results show similar parabolic velocity profiles for both blood and the Newtonian fluid for Re < 2200. However, differences were observed between blood and Newtonian fluid velocity profiles for larger Re. The Newtonian fluid had blunt-like velocity profiles starting at Re = 2403 ± 8 which indicated transition. In contrast, blood did not show this velocity profile change until Re = 2871 ± 104. The Newtonian fluid had large velocity fluctuations (root mean square (RMS) > 20%) with a maximum TKE near the pipe center at Re = 2316 ± 34 which indicated transition. In contrast, blood results showed the maximum TKE at Re = 2806 ± 109. Overall, the critical Re was delayed by ∼20% (p < 0.001) for blood compared to the Newtonian fluid. Thus, a Newtonian assumption for blood at flow conditions near transition could lead to large errors in velocity prediction for steady flow in a straight pipe. However, these results are specific to this pipe diameter and not generalizable since SR is highly dependent on pipe diameter. Further research is necessary to understand this relation in different pipe sizes, more complex geometries, and under pulsatile flow conditions.

Replication of a whole school ethos-changing intervention: different context, similar effects, additional insights.

BACKGROUND: Whole school, ethos-changing interventions reduce risk behaviours in middle adolescence, more than curriculum-based approaches. Effects on older ages are not known. We set out to replicate one of these interventions, Australia's Gatehouse Project, in a rural Canadian high school. METHODS: A guided, whole school change process sought to make students feel more safe, connected, and valued by: changes in teaching practices, orientation processes, professional development of staff, recognition and reward mechanisms, elevating student voice, and strategies to involve greater proactivity and participation. We conducted risk behaviour surveys in grades 10 to 12 before the intervention and 2 years afterwards, and social network analyses with the staff. Changes in health and health risk behaviours were assessed using chi-square. Interactions between the intervention and gender and between the intervention and school engagement were assessed using interaction terms in logistic regression models. Changes in the density of relationships among staff were tested with methods analogous to paired t-tests. RESULTS: Like Gatehouse, there was no statistically significant reduction in depressive symptoms or bullying, though the trend was in that direction. Among girls, there was a statistically significant decrease in low school engagement (45% relative reduction), and decreases in drinking (46% relative reduction), unprotected sex (61% relative reduction) and poor health (relative reduction of 73%). The reduction in drinking matched the national trend. Reductions in unprotected sex and poor health went against the national trend. We found no statistically significant changes for boys. The effects coincided with statistically significant increases in the densities of staff networks, indicating that part of the mechanism may be through relationships at school. CONCLUSIONS: A non-specific, risk protective intervention in the social environment of the school had a significant impact on a cluster of risk behaviours for girls. Results were remarkably like reports from similar school environment interventions elsewhere, albeit with different behaviours being affected. It may be that this type of intervention activates change processes that interact highly with context, impacting different risks differently, according to the prevalence, salience and distribution of the risk and the interconnectivity of relationships between staff and students. This requires further exploration.

Comorbid Problem Gambling and Major Depression in a Community Sample.

Major depression is among the most common comorbid conditions in problem gambling. However, little is known about the effects of comorbid depression on problem gambling. The present study examined the prevalence of current major depression among problem gamblers (N = 105) identified from a community sample of men and women in Alberta, and examined group differences in gambling severity, escape motivation for gambling, family functioning, childhood trauma, and personality traits across problem gamblers with and without comorbid depression. The prevalence of major depression among the sample of problem gamblers was 32.4%. Compared to problem gamblers without depression (n = 71), problem gamblers with comorbid depression (n = 34) reported more severe gambling problems, greater history of childhood abuse and neglect, poorer family functioning, higher levels of neuroticism, and lower levels of extraversion, agreeableness, and conscientiousness. Furthermore, the problem gamblers with comorbid depression had greater levels of childhood abuse and neglect, worse family functioning, higher neuroticism, and lower agreeableness and conscientiousness than a comparison sample of recreational gamblers with depression (n = 160). These findings underscore the need to address comorbid depression in assessment and treatment of problem gambling and for continued research on how problem gambling is related to frequently co-occurring disorders such as depression.

Pharmacotherapy of neuropsychiatric symptoms of dementia.

Approximately 5 million Americans have dementia, and many receive psychiatric medications. Management of such patients is complex and controversial, and it has become apparent that all potential pharmacological therapies present risks.

Evaluation of indirect transfer mechanisms of semen under varying test conditions.

There is limited data available on the subject of indirect transfer of non-visible body fluids, particularly semen, and often forensic science practitioner experience alone must be used to guide expectations. It can be difficult to assess the likelihood of proposed transfer scenarios without knowledge of how different variables can affect a transfer. The following work carried out by the Association of Forensic Service Providers UK and Ireland Body Fluid Forum explores how the features of transferred semen change with differences in the primary and secondary surface (porous and non- porous), different contact types (passive, pressure and pressure+) and with wet and dry primary stains. It was concluded that the primary surface type and whether the stain was wet or dry when contact occurred had the most significant effect on the transfer of semen, with wet transfers and transfers from the tested non-porous surface producing significantly more, and larger, visible stains under white light, stains with stronger fluorescence as viewed using Crime-lite® ML2, stains with stronger and faster acid phosphatase reactions and greater numbers of spermatozoa viewed using high power microscopy, compared to dry transfers and transfers from the tested porous surface. Pressure with movement transfers resulted in significantly more visible stains under white light and greater numbers of spermatozoa viewed using high power microscopy compared to passive transfers, however this only occurred when transfers were from a porous primary surface. The secondary surface type was not found to have a significant effect on the numbers of spermatozoa viewed using high power microscopy.

The role of funded partnerships in working towards decreasing COVID-19 vaccination disparities, United States, March 2021-December 2022.

During the COVID-19 vaccination rollout from March 2021- December 2022, the Centers for Disease Control and Prevention funded 110 primary and 1051 subrecipient partners at the national, state, local, and community-based level to improve COVID-19 vaccination access, confidence, demand, delivery, and equity in the United States. The partners implemented evidence-based strategies among racial and ethnic minority populations, rural populations, older adults, people with disabilities, people with chronic illness, people experiencing homelessness, and other groups disproportionately impacted by COVID-19. CDC also expanded existing partnerships with healthcare professional societies and other core public health partners, as well as developed innovative partnerships with organizations new to vaccination, including museums and libraries. Partners brought COVID-19 vaccine education into farm fields, local fairs, churches, community centers, barber and beauty shops, and, when possible, partnered with local healthcare providers to administer COVID-19 vaccines. Inclusive, hyper-localized outreach through partnerships with community-based organizations, faith-based organizations, vaccination providers, and local health departments was critical to increasing COVID-19 vaccine access and building a broad network of trusted messengers that promoted vaccine confidence. Data from monthly and quarterly REDCap reports and monthly partner calls showed that through these partnerships, more than 295,000 community-level spokespersons were trained as trusted messengers and more than 2.1 million COVID-19 vaccinations were administered at new or existing vaccination sites. More than 535,035 healthcare personnel were reached through outreach strategies. Quality improvement interventions were implemented in healthcare systems, long-term care settings, and community health centers resulting in changes to the clinical workflow to incorporate COVID-19 vaccine assessments, recommendations, and administration or referrals into routine office visits. Funded partners' activities improved COVID-19 vaccine access and addressed community concerns among racial and ethnic minority groups, as well as among people with barriers to vaccination due to chronic illness or disability, older age, lower income, or other factors.

Validity of the Problem Gambling Severity Index interpretive categories.

The Problem Gambling Severity Index (PGSI) is a widely used nine item scale for measuring the severity of gambling problems in the general population. Of the four gambler types defined by the PGSI, non-problem, low-risk, moderate-risk and problem gamblers, only the latter category underwent any validity testing during the scale's development, despite the fact that over 95% of gamblers fall into one of the remaining three categories. Using Canadian population data on over 25,000 gamblers, we conducted a comprehensive validity and reliability analysis of the four PGSI gambler types. The temporal stability of PGSI subtype over a 14-month interval was modest but adequate (intraclass correlation coefficient = 0.63). There was strong evidence for the validity of the non-problem and problem gambler categories however the low-risk and moderate-risk categories showed poor discriminant validity using the existing scoring rules. The validity of these categories was improved with a simple modification to the scoring system.

Do antidepressant medications work?

Treatment-resistant depression is extremely common-but does that mean there is no place for antidepressants?

Enzyme activity, DNA degradation and drying times of semen, saliva and vaginal material.

The stability of enzyme activity and the amount of detectable DNA within liquid samples of semen, saliva and vaginal material were tested across a number of days. The concentration of DNA within neat semen and saliva samples fell significantly after one week of refrigeration. No apparent change in acid phosphatase or amylase enzyme activity was observed in neat semen and saliva samples over 96 or 72 h respectively. Changes in the enzyme activity of most of the dilute semen and saliva samples, as well as the neat vaginal material sample, were noted after 24 h. The drying times and sizes of stains produced from various volumes of neat semen, saliva and vaginal material were tested on porous and non-porous surfaces at room temperature. Larger volumes of body fluid took longer to dry and generally resulted in larger stains. Body fluids on a non-porous surface took longer to dry than on the porous surface tested.

Analysis of responses to glyceryl trinitrate and sodium nitrite in the intact chest rat.

Responses to glyceryl trinitrate/nitroglycerin (GTN), S-nitrosoglutathione (GSNO), and sodium nitrite were compared in the intact chest rat. The iv injections of GTN, sodium nitrite, and GSNO produced dose-dependent decreases in pulmonary and systemic arterial pressures. In as much as cardiac output was not reduced, the decreases in pulmonary and systemic arterial pressures indicate that GTN, sodium nitrite, and GSNO have significant vasodilator activity in the pulmonary and systemic vascular beds in the rat. Responses to GTN were attenuated by cyanamide, but not allopurinol, whereas responses to nitrite formed by the metabolism of GTN were attenuated by allopurinol and cyanamide. The results with allopurinol and cyanamide suggest that only mitochondrial aldehyde dehydrogenase is involved in the bioactivation of GTN, sodium nitrite, and GSNO, whereas both pathways are involved in the bioactivation of nitrite anion in the intact rat. The comparison of vasodilator activity indicates that GSNO and GTN are more than 1000-fold more potent than sodium nitrite in decreasing pulmonary and systemic arterial pressures in the rat. Following administration of 1H-[1,2,4]-oxadizaolo[4,3-]quinoxaline-1-one (ODQ), responses to GTN were significantly attenuated, indicating that responses are mediated by the activation of soluble guanylyl cyclase. These data suggest that the reduction of nitrite to nitric oxide formed from the metabolism of GTN, cannot account for the vasodilator activity of GTN in the intact rat and that another mechanism; perhaps the formation of an S-NO, may mediate the vasodilator response to GTN in this species.

Effect of chronic sodium nitrite therapy on monocrotaline-induced pulmonary hypertension.

Pulmonary hypertension (PH) is a rare disorder that without treatment is progressive and often fatal within 3 years. The treatment of PH involves the use of a diverse group of drugs and lung transplantation. Although nitrite was once thought to be an inactive metabolite of endothelial-derived nitric oxide (NO), there is increasing evidence that nitrite may be useful in the treatment of PH, but the mechanism by which nitrite exerts its beneficial effect remains uncertain. The purpose of this study was to investigate the effect of chronic sodium nitrite treatment in a PH model in the rat. Following induction of PH with a single injection of monocrotaline, 60 mg; daily ip injections of sodium nitrite (3mg/kg) starting on day 14 and continuing for 21 days, resulted in a significantly lower pulmonary arterial pressure on day 35 when compared to values in untreated animals with monocrotaline-induced PH. In monocrotaline-treated rats, daily treatment with ip nitrite injections for 21 days decreased right ventricular mass and pathologic changes in small pulmonary arteries. Nitrite therapy did not change systemic arterial pressure or cardiac output when values were measured on day 35. The decreases in pulmonary arterial pressure in response to iv injections of sodium nitroprusside, sodium nitrite, and BAY 41-8543 were not different in rats with monocrotaline-induced pulmonary hypertension and rats with chronic nitrite therapy when compared to responses in animals in which pulmonary arterial pressure was increased with U46619. These findings are consistent with the hypothesis that the mechanisms that convert nitrite to vasoactive NO, activate soluble guanylyl cyclase and mediate the vasodilator response to NO or an NO derivative are not impaired. The present data are consistent with the results of a previous study in monocrotaline-induced PH in which systemic arterial pressure and cardiac output were not evaluated and are consistent with the hypothesis that nitrite is effective in the treatment of monocrotaline-induced PH in the rodent.

Peroxynitrite has potent pulmonary vasodilator activity in the rat.

Peroxynitrite (PN) worsens pathological conditions associated with oxidative stress. However, beneficial effects have also been reported. PN has been shown to demonstrate vasodilator as well as vasoconstrictor properties that are dependent upon the experimental conditions and the vascular bed studied. PN-induced vascular smooth muscle relaxation may involve the formation of nitric oxide (NO) donors. The present results show that PN has significant vasodilator activity in the pulmonary and systemic vascular beds, and that responses to PN were not attenuated by L-penicillamine (L-PEN), a PN scavenger, whereas responses to sodium nitroprusside (SNP) were decreased. PN had a small inhibitory effect on decreases in arterial pressure in response to the NO donors diethylammonium (Z)-1-(N,N-diethylamino)diazen-1-ium-1,2-diolate (DEA/NO) and S-nitrosoglutathione (GSNO). PN partially reversed hypoxic pulmonary vasoconstriction. PN responses were attenuated by the soluble guanylate cyclase (sGC) inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and responses to PN and the PN precursor, 3-morpholinosydnonimine (SIN-1), were different. These data show that PN has potent pulmonary vasodilator activity in the rat, and provide evidence that a PN interaction with S-nitrosothiols is not the major mechanism mediating the response. These data suggest that responses to PN are mediated by the activation of sGC, and that PN has a small inhibitory effect on NO responses.

The role of family, religiosity, and behavior in adolescent gambling.

Predictors of adolescent gambling behavior were examined in a sample of 436 males and females (ages 13-16). A biopsychosocial model was used to identify key variables that differentiate between non-gambling and gambling adolescents. Logistic regression found that, as compared to adolescent male non-gamblers, adolescent male gamblers were older, had more conflict in their family, were more likely to have used drugs, and have peers that gamble. Compared to adolescent female non-gamblers, adolescent female gamblers had more attention and thought problems, and scored higher on rule-breaking. For both males and females, religiosity was a protective factor against involvement in gambling. Some of the results are consistent with previous research, while some of these findings are unique to this study. These results shed light on factors to consider when developing programs to combat the negative impacts of gambling on adolescents.

Mitochondrial aldehyde dehydrogenase mediates vasodilator responses of glyceryl trinitrate and sodium nitrite in the pulmonary vascular bed of the rat.

It has been reported that mitochondrial aldehyde dehydrogenase (ALDH2) catalyzes the formation of glyceryl dinitrate and inorganic nitrite from glyceryl trinitrate (GTN), leading to an increase in cGMP and vasodilation in the coronary and systemic vascular beds. However, the role of nitric oxide (NO) formed from nitrite in mediating the response to GTN in the pulmonary vascular bed is uncertain. The purpose of the present study was to determine if nitrite plays a role in mediating vasodilator responses to GTN. In this study, intravenous injections of GTN and sodium nitrite decreased pulmonary and systemic arterial pressures and increased cardiac output. The decreases in pulmonary arterial pressure under baseline and elevated tone conditions and decreases in systemic arterial pressure in response to GTN and sodium nitrite were attenuated by cyanamide, an ALDH2 inhibitor, whereas responses to the NO donor, sodium nitroprusside (SNP), were not altered. The decreases in pulmonary and systemic arterial pressure in response to GTN and SNP were not altered by allopurinol, an inhibitor of xanthine oxidoreductase, whereas responses to sodium nitrite were attenuated. GTN was approximately 1,000-fold more potent than sodium nitrite in decreasing pulmonary and systemic arterial pressures. These results suggest that ALDH2 plays an important role in the bioactivation of GTN and nitrite in the pulmonary and systemic vascular beds and that the reduction of nitrite to vasoactive NO does not play an important role in mediating vasodilator responses to GTN in the intact chest rat.

Analysis of responses to the Rho-kinase inhibitor Y-27632 in the pulmonary and systemic vascular bed of the rat.

Responses to the Rho kinase inhibitor Y-27632 were investigated in the anesthetized rat. Under baseline conditions intravenous injections of Y-27632 decreased pulmonary and systemic arterial pressures and increased cardiac output. The decreases in pulmonary arterial pressures were enhanced when baseline tone was increased with U-46619, and under elevated tone conditions Y-27632 produced similar percent decreases in pulmonary and systemic arterial pressures. Injections of Y-27632 prevented and reversed the hypoxic pulmonary vasoconstrictor response. The increase in pulmonary arterial pressure in response to ventilation with a 10% O(2)-90% N(2) gas mixture was not well maintained during the period of hypoxic exposure. Treatment with the nitric oxide (NO) synthase (NOS) inhibitor nitro-l-arginine methyl ester (l-NAME) increased pulmonary arterial pressure and prevented the decline or fade in the hypoxic pulmonary vasoconstrictor response. The hypoxic pulmonary vasoconstrictor response was reversed by Y-27632 in control and in l-NAME-treated animals. The Rho kinase inhibitor attenuated increases in pulmonary arterial pressures in response to intravenous injections of serotonin, angiotensin II, and Bay K 8644. Y-27632, sodium nitrite, and BAY 41-8543, a guanylate cyclase stimulator, decreased pulmonary and systemic arterial pressures and vascular resistances in monocrotaline-treated rats. These data suggest that Rho kinase is involved in the regulation of baseline tone and in the mediation of pulmonary vasoconstrictor responses. The present data suggest that the hypoxic pulmonary vasoconstrictor response is modulated by the release of NO that mediates the nonsustained component of the response in the anesthetized rat. These data suggest that Rho kinase and NOS play important roles in the regulation of vasoconstrictor tone in physiological and pathophysiological states and that monocrotaline-induced pulmonary hypertension can be reversed by agents that inhibit Rho kinase, generate NO, or stimulate soluble guanylate cyclase.

Intracavernosal administration of sodium nitrite as an erectile pharmacotherapy.

It has been reported that sodium nitrite (NaNO2) can act as a storage form of nitric oxide (NO) that can have beneficial pharmacologic actions. The present study was undertaken to investigate the effects of NaNO2 on erectile function in the rat. The intracavernosal (i.c.) injection of NaNO2 produced dose-related increases in i.c. pressure and decreases in systemic arterial pressure. NaNO2 was 1000-fold less potent than sodium nitroprusside in increasing i.c. pressure. Increases in i.c. pressure in response to NaNO2 were attenuated by the nitric oxide synthase (NOS) inhibitor N-nitro-L-arginine methyl ester (L-NAME). The increases in i.c. pressure in response to NaNO2 were not altered by the xanthine oxidoreductase inhibitor allopurinol. The decreases in systemic arterial pressure in response to i.c. injections of NaNO2 were attenuated by allopurinol and were either unchanged or increased by L-NAME. These data suggest that NaNO2 is converted to vasoactive NO in the corpora cavernosum and systemic vascular bed of the rat by different mechanisms. The present data suggest that the conversion of NaNO2 to vasoactive NO is mediated by NOS in the corpora cavernosum and by xanthine oxidoreductase in the systemic vascular bed of the rat. These data show NaNO2 can serve as a NO donor that increases erectile activity in the rat.