Opioids in the systemic hemodynamic and renal responses to stress in spontaneously hypertensive rats.

Abstract

Endogenous opioid peptides have been implicated in the regulation of cardiovascular and renal function. We tested this hypothesis by examining whether the opioid antagonist naloxone alters the cardiovascular or renal responses produced by environmental stress (air stress) in conscious spontaneously hypertensive rats (SHR). Before naloxone administration, air stress produced significant increases in heart rate, mean arterial pressure, and renal sympathetic nerve activity, and it caused a decrease in urinary sodium excretion. After intravenous and intracerebroventricular administration of naloxone, the air stress-induced pressor and antinatriuretic responses were inhibited. Subsequent studies with a different opioid antagonist, the quaternary compound naltrexone methylbromide, also showed inhibition of the air stress-induced pressor and antinatriuretic responses and demonstrated opioid receptor specificity of this inhibition. Furthermore, since only intracerebroventricular and not intravenous administration of naltrexone methylbromide inhibited the pressor and antinatriuretic responses to air stress, a central nervous system site of action was established. The opioid antagonists caused inhibition of the pressor and antinatriuretic responses to air stress without affecting the air stress-induced increase in renal sympathetic nerve activity. Our investigations indicate that central endogenous opioid peptides contribute to the pressor and antinatriuretic responses that occur in conscious SHR during acute environmental stress. {Hypertension 1989; 13:808-816)

Effects of opioid peptides on neural control of renal function in spontaneously hypertensive rats.

“…Inhibition of a response by naloxone is generally considered evidence for interaction of opioid receptors with endogenous opioids in the response, 21 particularly if low doses are used, as in the present study. Thus, the results of these studies, together with the previous finding that naloxone also abolishes the antinatriuresis to air jet stress without altering the renal sympathoexcitatory response, 5 provide further evidence that endogenous opioidergic systems influence mechanisms that regulate the renal tubular sodium reabsorption response during conditions of increased efferent renal sympathetic nerve activity.…”

“…Administration of the opioid receptor antagonists naloxone (intravenously) or naltrexone methylbromide (intracerebroventricularly) to conscious SHR abolishes the decrease in urinary sodium excretion without affecting the increase in efferent renal sympathetic nerve activity. 5 These opioid receptor antagonists do not affect urinary sodium excretion during air jet stress under conditions in which the influence of the renal sympathetic nerves had been removed by previous bilateral renal denervation. 5 Thus, an interaction between the renal sympathetic nerves and endogenous opioidergic systems is suggested in mediating the antinatriuretic response to acute environmental stimulation.…”

“…5 These opioid receptor antagonists do not affect urinary sodium excretion during air jet stress under conditions in which the influence of the renal sympathetic nerves had been removed by previous bilateral renal denervation. 5 Thus, an interaction between the renal sympathetic nerves and endogenous opioidergic systems is suggested in mediating the antinatriuretic response to acute environmental stimulation. From these cited findings it can be hypothesized that opioids might modulate neurotransmitter release from renal sympathetic nerves and thus modify renal function during conditions of increased efferent renal sympathetic nerve activity.…”

“…2 Moreover, intravenous administration of the opioid antagonist naloxone also prevents the antinatriuresis but does not affect the renal sympathoexcitatory response. 5 In bilaterally renal-denervated SHR exposed to air jet stress, the urinary sodium excretion response is not altered by naloxone. 5 Thus, these findings suggest that expression of the antinatriuretic response evoked by the air jet stress involves activation of endogenous opioidergic systems.…”

“…5 In bilaterally renal-denervated SHR exposed to air jet stress, the urinary sodium excretion response is not altered by naloxone. 5 Thus, these findings suggest that expression of the antinatriuretic response evoked by the air jet stress involves activation of endogenous opioidergic systems. Furthermore, it appears that these two systems, a functional opioidergic system and an intact renal innervation, interact to mediate the antinatriuretic response to this acute environmental stress stimulus.…”