Effect of intranasal histamine on nasal mucosal blood flow and the antidiuretic activity of desmopressin

Abstract

The effects of exogenous histamine on nasal mucosal blood flow and the systemic activity of intranasally administered desmopressin, a vasopressin analogue, were studied in normal volunteers. Ten subjects received either saline or histamine (1, 20, 100, and 500 μg) by intranasal spray. Maximal nasal mucosal blood flow response, determined by laser doppler velocimetry, demonstrated a significant (P < 0.05) linear relationship to histamine dose. Eight additional subjects received each of the following intranasal treatments: 20 μg histamine followed by 10 μg desmopressin; normal saline followed by 10 μg desmopressin; 20 μg histamine followed by vehicle; or normal saline and vehicle. Nasal blood flow was determined before and after each treatment. Desmopressin activity was assessed by measuring urine osmolality, flow rate, electrolyte, and creatinine concentration for 24 h after each treatment. The effect of histamine and desmopressin was greater than desmopressin alone, with respect to nasal blood flow response (103 ± 24 vs. 4 ± 17%, mean ± SEM, P < 0.02), initial urine osmolality (520 ± 123 vs. 333 ± 75 mosM, P < 0.03), urine electrolyte (potassium, 45 ± 11 vs. 28 ± 7 meq/liter; sodium, 68 ± 21 vs. 36 ± 8 meq/liter, P < 0.03) and creatinine concentrations (95 ± 23 vs. 60 ± 13 mg/dl, P < 0.03), and the duration of decrease in urine flow rate compared with saline and vehicle. These results suggest that the systemic activity of intranasal desmopressin is enhanced by increasing local nasal blood flow and are consistent with increased transnasal absorption of the peptide.