Effect of intranasal histamine on nasal mucosal blood flow and the antidiuretic activity of desmopressin.
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 micrograms) by intranasal spray. Maximal nasal mucosal blood flow response, determined by laser doppler velocimetry, demonstrated a significant (P less than 0.05) linear relationship to histamine dose. Eight additional subjects received each of the following intranasal treatments: 20 micrograms histamine followed by 10 micrograms desmopressin; normal saline followed by 10 micrograms desmopressin; 20 micrograms 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 less than 0.02), initial urine osmolality (520 +/- 123 vs. 333 +/- 75 mosM, P less than 0.03), urine electrolyte (potassium, 45 +/- 11 vs. 28 +/- 7 meq/liter; sodium, 68 +/- 21 vs. 36 +/- 8 meq/liter, P less than 0.03) and creatinine concentrations (95 +/- 23 vs. 60 +/- 13 mg/dl, P less than 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.
D000281:Administration, Intranasal; D000328:Adult; D003894:Deamino Arginine Vasopressin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004357:Drug Synergism; D005260:Female; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D007671:Kidney Concentrating Ability / Q000187:drug effects; D008297:Male; D009297:Nasal Mucosa / Q000098:blood supply*; D009994:Osmolar Concentration; D012039:Regional Blood Flow / Q000187:drug effects; D014556:Urine / Q000378:metabolism; D014667:Vasopressins / Q000037:antagonists & inhibitors*
D014667:Vasopressins; D006632:Histamine; D003894:Deamino Arginine Vasopressin