The opioid peptides. A role in hypertension?

Area of Science:

• Cardiovascular Physiology
• Neuropharmacology
• Hypertension Pathogenesis

Background:

• The endogenous opioid system's role in blood pressure regulation is complex.
• Evidence suggests involvement in hypertension pathogenesis, but clinical translation is challenging.

Purpose of the Study:

• To review evidence implicating the endogenous opioid system in human hypertension.
• To explore the complexities of opioid receptor subtypes in cardiovascular control.

Main Methods:

• Review of biochemical, physiological, pharmacological, and behavioral studies.
• Analysis of data from in vitro/in vivo systems, animal models, and human essential hypertension studies.

Main Results:

• Opioid peptides and receptors are present in cardiovascular control sites, showing potent responses in animals.
• Nonselective opioid antagonists lack consistent antihypertensive effects in animals and humans.
• Differential effects of mu- (pressor) and kappa- (depressor) opioid receptors complicate therapeutic strategies.

Conclusions:

• The complexity of opioid receptor subtypes (mu vs. kappa) explains the lack of effect with nonselective antagonists.
• Selective mu-antagonists or kappa-agonists, or combined mu-antagonist/kappa-agonist drugs, may offer future antihypertensive strategies.
• Further development of selective opioid receptor modulators is needed to validate this hypothesis.