Vascular actions of natriuretic peptides

Abstract. Natriuretic peptides play important roles in the regulation of cardiovascular homeostasis. The endocrine actions of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) complement the paracrine effects of C-type natriuretic peptide (CNP) and urodilatin to regulate vascular smooth muscle tone, uid and electrolyte balance and cardiac morphology. As a consequence, aberrant natriuretic peptide production and/or activity have been linked to a number of cardiovascular disorders and interventions that selectively modulate these vasoactive peptides may be of therapeutic benet. This review will outline the structure, expression and vascular actions of natriuretic peptides and their endogenous receptors and highlight recent work that has revealed important interactions between the cyclic GMP producing particulate and soluble guanylate cyclases, thereby linking the cardiovascular actions of natriuretic peptides and nitric oxide, and a role for CNP as an endothelium-derived hyperpolarising factor (EDHF).     

Development of the Pharm-SAVES educational module for gatekeeper suicide prevention training for community pharmacy staff

Introduction

Pharmacists are one of the most accessible health professionals in the United States, who, with training, may serve as gatekeepers who recognize suicide warning signs and refer at-risk individuals to care. Our objective was to codesign a 30-min online gatekeeper training module (Pharm-SAVES) specifically for community pharmacy staff.

Methods

Over a period of 8 months, a nine-member pharmacy staff stakeholder panel and the Finger Lakes (New York) Veterans Research Engagement Review Board each worked with the study team to codesign Pharm-SAVES. Formative data from previous interviews with community pharmacists were presented to the panels and guided website development.

Results

Four key topics were identified for brief skills-based modules that could be delivered asynchronously online. To help pharmacy staff understand their opportunities as gatekeepers in suicide prevention, statistics and statements from the Joint Commission and pharmacy professional organizations were highlighted in Module 1 (‘Why Me?’). Module 2 (‘What can I do?’) presents the five gatekeeping steps (SAVES): (1) Recognize suicide warning S igns, (2) A sk if someone is considering suicide, (3) V alidate feelings, (4) E xpedite referral, and (5) S et a reminder to follow-up. Module 3 (‘How does it work?’) provides three video scenarios modeling SAVES steps and two interactive video cases for participant practice. Module 3 demonstrates use of the 24/7 National Suicide Prevention Lifeline, including the DOD/VA Crisis Line. Module 4 (Resources) includes links to national resources and a searchable zip code-based provider directory. Pharm-SAVES was codesigned with pharmacy and veteran stakeholders to deliver brief, skills-focused, video-based interactive training that is feasible to implement in busy community pharmacy settings.

Conclusion

Pharm-SAVES is a brief, online suicide prevention gatekeeper training program codesigned by researchers, community pharmacy and veteran stakeholders. By actively engaging stakeholders at each stage of the design process, we were able to create training content that was not only realistic but more relevant to the needs of pharmacy staff. Currently, Pharm-SAVES is being evaluated in a pilot randomized controlled trial for changes in pharmacy staff suicide prevention communication behaviors.

Patient or Public Contribution

Stakeholder engagement was purposefully structured to engage pharmacy staff and pharmacy consumers, with multiple opportunities for study contribution. Likewise, the involvement of patient/public contribution was paramount in study design and overall development of our study team.     

Quality of life following epilepsy surgery for children with tuberous sclerosis complex

Parents of children with tuberous sclerosis complex who underwent multistage resections for treatment of refractory seizures were offered a telephone questionnaire regarding quality of life (QOL) of child and family since surgery. Of 53 families, 39 responded. Age at epilepsy onset was birth to 3 months. Average duration of epilepsy before the first surgery was 5.1 years, and average age at surgery was 5.8. The average follow-up was 3.9. Seventy-seven percent had a >90% reduction in disabling seizures. In all outcome categories, 46-85% had at least a moderate improvement in QOL. There was a significant correlation between QOL variables and Engel outcome class. Despite the potential burden posed by the aggressive surgical approach, including multiple surgeries and long hospitalization periods, 94% of parents would choose the same course once again. We conclude that aggressive surgical treatment of tuberous sclerosis complex-related refractory seizures is associated with significant control of epilepsy as well as improved QOL for the patient and family.     

Concentration of dimethyl-L-arginine in the plasma of patients with end-stage renal failure

Abstract. N^GN^Gdimethyl-L-arginine (asymmetric dimethyl-L-arginineADMA) and N^GN^G dimethyl-L-arginine (symmetric dimethyl-L-arginine;SDMA) are naturally occurring analogues of L-arginine, the substratefor nitric oxide (NO) synthesis. ADMA is a potent inhibitorof NO synthesis, and accumulates in the plasma of patients withrenal failure. However the precise concentration of ADMA andSDMA in renal patients is still controversial. This study wasperformed to measure plasma ADMA and SDMA concentrations bytwo different HPLC techniques in nine healthy controls and 10uraemic subjects, and to investigate the effects of haemodialysis.In controls, the mean (±SEM) plasma concentrations ofADMA and SDMA were 0.36±0.09 and 0.39±0.05 µmol/lrespectively, yielding an ADMA/SDMA ratio of 1.2± 0.17.In uraemic patients, the plasma concentrations of ADMA and SDMAwere 0.9±0.08 µmol/l (P<0.001 compared to controls)and 3.4±0.3 µmol/l (P<0.001 compared to controls)with an ADMA/SDMA ratio of 0.27±0.015 (P<0.001). Inthe course of one 4 h haemodialysis session, ADMA concentrationsdecreased from 0.99±0.13 to 0.77±0.3 µmol/land SDMA concentrations from 3.38±0.44 to 2.27±0.21µmol/l. The plasma ADMA/creatinine ratio tended to increasefrom 1.26±0.20 x 10^–3 to 2.01±0.41 x 10^–3It is concluded that there is a modest (3-fold) but definiteincrease in plasma ADMA concentration in uraemic patients comparedto controls. SDMA accumulates to a greater degree (8-fold increase)and more closely parallels creatinine concentration than ADMA.The change in the ADMA/SDMA ratio is not accounted for by greaterrenal or dialysis clearance of ADMA, and, even though alternativeexplanations are not excluded, greater metabolism of ADMA thanSDMA is the most likely explanation. Although small in magnitude,the increase in ADMA concentration might be biologically significant.     

Changes in endothelium-dependent vasodilatation and alpha-adrenergic responses in resistance vessels during the menstrual cycle in healthy women

During the menstrual cycle, changes in endothelium-dependent vasodilatation have been demonstrated in conduit vessels in vivo, but responses in resistance vessels have not been studied. The aim of this study was to examine endothelium-dependent vasodilatation, the effects of local nitric oxide synthesis, and alpha-adrenergic constriction in resistance vessels during the menstrual cycle in 15 healthy female volunteers (mean age, 28.07 +/- 2.1 yr). Forearm blood flow in response to intrabrachial infusion of bradykinin (10, 30, and 100 pmol/min; endothelium-dependent vasodilator), glyceryl trinitrate (4, 8, and 16 nmol/min; endothelium-independent vasodilator), noradrenaline (60, 120, and 240 pmol/min; alpha-adrenergic receptor agonist), and N(G)-monomethyl-L-arginine (1, 2, and 4 micromol/min; nitric oxide synthase inhibitor) was assessed by venous occlusion plethysmography. All subjects were studied in early menstrual phase (days 1--4) and midcycle (days 10-13). Vasodilator response to bradykinin, expressed as the within-subject mean difference in the area under the dose-response curve between phases, was significantly increased at midcycle compared with that in the early menstrual phase (486.5 +/- 165.0; P = 0.01), whereas there was no significant difference in response to glyceryl trinitrate (185.8 +/- 239.0; P = 0.45). The vasoconstrictor response to noradrenaline was significantly greater at midcycle (97.1 +/- 39.4; P = 0.027), but the response to N(G)-monomethyl-L-arginine was not significantly different (17.5 +/- 35.2; P = 0.63). Serum estradiol was approximately 3-fold higher at midcycle, with a mean difference of 252.3 +/- 56.0 pmol/L (P = 0.0005). Progesterone concentrations were not significantly different (-0.11 +/- 0.1 nmol/L; P = 0.28). Differences in endogenous estrogen levels between menstrual phases may underlie changes in bradykinin and noradrenaline responses. If exogenous estrogens have similar effects, the balance of these two opposing actions may determine whether estrogen replacement in postmenopausal women has beneficial or harmful effects on the vasculature.