Hypothalamic kinin B1 receptor mediates orexin system hyperactivity in neurogenic hypertension.

Brain orexin system hyperactivity contributes to neurogenic hypertension. We previously reported upregulated neuronal kinin B1 receptor (B1R) expression in hypertension. However, the role of central B1R activation on the orexin system in neurogenic hypertension has not been examined. We hypothesized that kinin B1R contributes to hypertension via upregulation of brain orexin-arginine vasopressin signaling. We utilized deoxycorticosterone acetate (DOCA)-salt hypertension model in wild-type (WT) and B1R knockout (B1RKO) mice. In WT mice, DOCA-salt-treatment increased gene and protein expression of orexin A, orexin receptor 1, and orexin receptor 2 in the hypothalamic paraventricular nucleus and these effects were attenuated in B1RKO mice. Furthermore, DOCA-salt- treatment increased plasma arginine vasopressin levels in WT mice, but not in B1RKO mice. Cultured primary hypothalamic neurons expressed orexin A and orexin receptor 1. B1R specific agonist (LDABK) stimulation of primary neurons increased B1R protein expression, which was abrogated by B1R selective antagonist R715 but not by the dual orexin receptor antagonist, ACT 462206, suggesting that B1R is upstream of the orexin system. These data provide novel evidence that B1R blockade blunts orexin hyperactivity and constitutes a potential therapeutic target for the treatment of salt-sensitive hypertension.

Evaluation of a modified infraorbital approach for a maxillary nerve block for rhinoscopy with nasal biopsy of dogs.

OBJECTIVE To determine whether a maxillary nerve block via a modified infraorbital approach, applied before rhinoscopy and nasal biopsy of dogs, would decrease procedural nociception, minimize cardiorespiratory anesthetic effects, and improve recovery quality. ANIMALS 8 healthy adult hound-type dogs PROCEDURES In a crossover study, dogs received 0.5% bupivacaine (0.1 mL/kg) or an equivalent volume of saline (0.9% NaCl) solution as a maxillary nerve block via a modified infraorbital approach. A 5-cm, 20-gauge over-the-needle catheter was placed retrograde within each infraorbital canal, and bupivacaine or saline solution was administered into each pterygopalatine region. Rhinoscopy and nasal biopsy were performed. Variables monitored included heart rate, systolic arterial blood pressure (SAP), mean arterial blood pressure (MAP), diastolic arterial blood pressure (DAP), plasma cortisol and norepinephrine concentrations, purposeful movement, and pain scores. After a 14-day washout period, the other treatment was administered on the contralateral side, and rhinoscopy and nasal biopsy were repeated. RESULTS SAP, MAP, and DAP were significantly higher for the saline solution treatment than for the bupivacaine treatment, irrespective of the time point. Plasma cortisol concentrations after saline solution treatment were significantly higher 5 minutes after nasal biopsy than at biopsy. Heart rate, norepinephrine concentration, purposeful movement, and pain score were not significantly different between treatments. CONCLUSIONS AND CLINICAL RELEVANCE Maxillary nerve block via a modified infraorbital approach prior to rhinoscopy and nasal biopsy reduced procedural nociception as determined on the basis of blood pressures and plasma cortisol concentrations during anesthesia. These findings warrant further evaluation in dogs with nasal disease.