Background/Methods: We have examined the hypothesis that cyst formation is key in the pathogenesis of cardiovascular disease in a Lewis polycystic kidney (LPK) model of autosomal-recessive polycystic kidney disease (ARPKD), by determining the relationship between cyst development and indices of renal function and cardiovascular disease. Results: In the LPK (n = 35), cysts appear at week 3 (1.1 ± 0.1 mm) increasing to week 24 (2.8 ± 2 mm). Immunostaining for nephron-specific segments indicate cysts develop predominantly from the collecting duct. Cyst formation preceded hypertension (160 ± 22 vs. Lewis control 105 ± 20 mm Hg systolic blood pressure (BP), n = 12) at week 6, elevated creatinine (109 ± 63 vs. 59 ± 6 µmol/l, n = 16) and cardiac mass (0.7 vs. 0.4% bodyweight, n = 15) at week 12, and left ventricular hypertrophy (2,898 ± 207 vs. 1,808 ± 192 µm, n = 14) at week 24 (all p ≤ 0.05). Plasma-renin activity and angiotensin II were reduced in 10- to 12-week LPK (2.2 ± 2.9 vs. Lewis 11.9 ± 4.9 ng/ml/h, and 25.0 ± 19.1 vs. 94.9 ± 64.4 pg/ml, respectively, n = 26, p ≤ 0.05). Ganglionic blockade (hexamethonium 3.3 mg/kg) significantly reduced mean BP in the LPK (52 vs. Lewis 4%, n = 9, p ≤ 0.05). Conclusion: Cyst formation is a key event in the genesis of hypertension while the sympathetic nervous system is important in the maintenance of hypertension in this model of ARPKD.

Veterinarians are more likely to experience mood disorders and suicide than other occupational groups (Fritschi, Morrison, Shirangi & Day, 2009; Platt, Hawton, Simkin, & Mellanby, 2010). The performance of euthanasia has been implicated as contributing determinately to the prevalence of suicide risk and psychological distress in veterinarians (Bartram & Baldwin, 2008, 2010). In contrast, the application of psychological approaches would suggest a possible protective role for euthanasia administration. This paper is the first to investigate the association between euthanasia-administration frequency and depressed mood and suicide risk. A cross-sectional survey sampled 540 Australia-registered veterinarians (63.8% women), ranging in age from 23 to 74. Results revealed that the administration of objectionable euthanasia (i.e., euthanasia that the veterinarian disagreed with) was not related to our mental health variables. In contrast, overall euthanasia frequency had a weak positive linear relationship with depression. Moreover, overall euthanasia frequency moderated the impact of depression on suicide risk. The nature of this moderation suggested that average frequency per week of performing euthanasia attenuated the relationship between depressed mood and suicide risk. The implications of these findings and directions for further research are discussed.

Breathing results from sequential recruitment of muscles in the expiratory, inspiratory, and postinspiratory (post-I) phases of the respiratory cycle. Here we investigate whether neurons in the medullary intermediate reticular nucleus (IRt) are components of a central pattern generator (CPG) that generates post-I activity in laryngeal adductors and vasomotor sympathetic nerves and interacts with other members of the central respiratory network to terminate inspiration. We first identified the region of the (male) rat IRt that contains the highest density of lightly cholinergic neurons, many of which are glutamatergic, which aligns well with the putative postinspiratory complex in the mouse (Anderson et al., 2016). Acute bilateral inhibition of this region reduced the amplitudes of post-I vagal and sympathetic nerve activities. However, although associated with reduced expiratory duration and increased respiratory frequency, IRt inhibition did not affect inspiratory duration or abolish the recruitment of post-I activity during acute hypoxemia as predicted. Rather than representing an independent CPG for post-I activity, we hypothesized that IRt neurons may instead function as a relay that distributes post-I activity generated elsewhere, and wondered whether they could be a site of integration for para-respiratory CPGs that drive the same outputs. Consistent with this idea, IRt inhibition blocked rhythmic motor and autonomic components of fictive swallow but not swallow-related apnea. Our data support a role for IRt neurons in the transmission of post-I and swallowing activity to motor and sympathetic outputs, but suggest that other mechanisms also contribute to the generation of post-I activity.SIGNIFICANCE STATEMENTInteractions between multiple coupled oscillators underlie a three-part respiratory cycle composed from inspiratory, postinspiratory (post-I), and late-expiratory phases. Central post-I activity terminates inspiration and activates laryngeal motoneurons. We investigate whether neurons in the intermediate reticular nucleus (IRt) form the central pattern generator (CPG) responsible for post-I activity. We confirm that IRt activity contributes to post-I motor and autonomic outputs, and find that IRt neurons are necessary for activation of the same outputs during swallow, but that they are not required for termination of inspiration or recruitment of post-I activity during hypoxemia. We conclude that this population may not represent a distinct CPG, but instead may function as a premotor relay that integrates activity generated by diverse respiratory and nonrespiratory CPGs.