Pharmacokinetics and biological actions of subcutaneously administered human brain natriuretic peptide.

Human brain natriuretic peptide (hBNP) has demonstrated favorable hemodynamic effects in patients with congestive heart failure; however, the peptidic nature of this compound has focused clinical testing on protocols involving intravenous delivery. We have studied subcutaneous delivery as an alternative method of administering hBNP. Administration of 30 microgram/kg hBNP by either subcutaneous or intravenous delivery protocols resulted in significant hBNP-immunoreactive material in the plasma with area under the plasma concentration-time curve values of 310 +/- 20 nmolxmins/liter and 187 +/- 47 nmolxmins/liter, respectively. Plasma cyclic GMP, a surrogate marker of activation of the biological receptor for hBNP, was elevated for a longer period of time following subcutaneous delivery compared with intravenous delivery. Subcutaneous delivery of 30 microg/kg hBNP resulted in natriuresis, diuresis and reduced systolic blood pressure in anesthetized normotensive rabbits, effects similar in magnitude yet prolonged in duration compared with those elicited by the same dose of hBNP delivered intravenously. Systolic blood pressure following hBNP treatment remained below base-line values for 50 and 150 min following intravenous and subcutaneous delivery protocols, respectively. These results suggests that subcutaneous delivery of hBNP may be a viable therapeutic alternative to intravenous modes of delivery.

Human brain natriuretic peptide reduces blood pressure in normotensive and acute norepinephrine-induced hypertensive rabbits.

Human brain natriuretic peptide (hBNP) is a cardiac-derived peptide hormone with potent hemodynamic and renal effects in dogs, monkeys, and humans, but not in rats. At present there is no small animal model to study the actions of hBNP. These studies describe the effects of hBNP in New Zealand White rabbits in normotensive and acute norepinephrine-induced hypertensive states. Intravenous administration of hBNP (1, 3, 10, and 30 microg/kg) to anesthetized rabbits resulted in a dose-dependent diuresis and natriuresis and a decrease in systolic blood pressure. Bolus administration of hBNP resulted in a time- and dose-dependent accumulation of plasma cyclic GMP, consistent with activation of a particulate guanylyl cyclase receptor. The hemodynamic actions of hBNP suggest clinical utility for the management of acute hypertension associated with numerous surgical procedures, a condition linked to catecholamine activation. In rabbits with norepinephrine-induced acute hypertension, bolus and continuous infusion of hBNP markedly reduced blood pressure. These studies demonstrate that the rabbit is a useful species to study the hemodynamic and renal effects of hBNP and that this peptide may have therapeutic utility for the acute reduction of hypertension associated with catecholamine activation.