5-Aminolevulinic acid hydrochloride enhances bupivacaine-induced hypotension in spontaneously hypertensive rats

J Pharmacol Sci. 2023 May;152(1):22-29. doi: 10.1016/j.jphs.2023.02.007. Epub 2023 Feb 24.

Abstract

Purpose: Oral administration of 5-aminolevulinic acid hydrochloride (5-ALA-HCl) has been reported to enhance the hypotensive effects associated with anesthetics, especially in elderly hypertensive patients treated with antihypertensive agents. The present study aimed to clarify the effects of antihypertensive-agent- and anesthesia-induced hypotension by 5-ALA-HCl in spontaneously hypertensive rats (SHRs).

Methods: We measured blood pressure (BP) of SHRs and normotensive Wistar Kyoto (WKY) rats treated with amlodipine or candesartan before and after administration of 5-ALA-HCl. We also investigated the change in BP following intravenous infusion of propofol and intrathecal injection of bupivacaine in relation to 5-ALA-HCl administration.

Findings: Oral administration of 5-ALA-HCl significantly reduced BP in SHRs and WKY rats with amlodipine and candesartan. Infusion of propofol significantly reduced BP in SHRs treated with 5-ALA-HCl. Intrathecal injection of bupivacaine significantly declined SBP and DBP in both SHRs and WKY rats treated with 5-ALA-HCl. The bupivacaine-induced decline in SBP was significantly larger in SHRs compared with WKY rats.

Conclusion: These findings suggest that 5-ALA-HCl does not affect the antihypertensive agents-induced hypotensive effect, but enhances the bupivacaine-induced hypotensive effect, especially in SHRs, indicating that 5-ALA may contribute to anesthesia-induced hypotension via suppression of sympathetic nerve activity in patients with hypertension.

Keywords: 5-Aminolevulinic acid; Bupivacaine; Hypotension; Propofol; Spontaneous hypertensive rats.

MeSH terms

  • Aminolevulinic Acid / adverse effects
  • Amlodipine / adverse effects
  • Animals
  • Antihypertensive Agents / adverse effects
  • Blood Pressure
  • Bupivacaine
  • Hypertension* / chemically induced
  • Hypertension* / drug therapy
  • Hypotension* / chemically induced
  • Hypotension* / drug therapy
  • Hypotension, Controlled*
  • Propofol* / pharmacology
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY

Substances

  • candesartan
  • Antihypertensive Agents
  • Aminolevulinic Acid
  • Bupivacaine
  • Propofol
  • Amlodipine