Role of L-type calcium channels in altered microvascular responses to propofol in hypertension.

Abstract

BACKGROUND:

Propofol acts as an L-type calcium channel (LTCC) antagonist to decrease peripheral resistance and initiate hypotension. This study investigated LTCC sensitivity/expression in hypertension and the role of LTCCs in exaggerated hypotension to propofol in this situation.

METHODS:

Age-matched 12- to 15-week-old normotensive rats [male Wistar Kyoto (WKY)] and spontaneously hypertensive rats (SHR) were used. Propofol (10 mg kg(-1), 10-50 mg kg(-1) h(-1) i.v.) was administered and the mesenteric microcirculation (<70 µm) observed with fluorescent in vivo microscopy using fluorescein isothiocyanate-conjugated bovine serum albumin (100 mg kg(-1) i.v.). Western blotting was used to measure tissue expression of the α(1C) LTCC subtype. Pressure myography was used to assess isolated mesenteric arterioles (<350 µm) in response to BAYK8644 (0.1 nM-1 µM), a specific LTCC channel agonist.

RESULTS:

Propofol dilated isolated arterioles {336.6 µM [mean (sd) change 16.2 (5.8)%]}. However, constriction to BAYK8644 was reduced at this concentration of propofol [EC(50)=8.3 (0.1) log mol(-1)] compared with controls [7.4 (0.1) log mol(-1), P<0.05], suggesting that propofol inhibited LTCCs. The sensitivity of LTCCs increased during hypertension, as in vivo there was a greater increase in mean arterial pressure (MAP) to BAYK8644 [10 µg kg(-1), WKY: 59.5 (9.3)%; SHR: 97.7 (6.3)%, P<0.05] with exaggerated constriction of arterioles [10 µg kg(-1), WKY: 9.1 (2.5)%; SHR: 19.1 (2.6)%, P<0.05]. Propofol also decreased MAP in SHR over time (P<0.05), but remained unchanged in WKY. Using western blotting, expression of α(1C) was greater in SHR compared with WKY (P<0.05).

CONCLUSIONS:

Propofol acts via LTCC channels, with increased channel expression and sensitivity in genetically hypertensive rats. We suggest that increased sensitivity and expression of LTCCs may be a mechanism for exaggerated hypertension during propofol anaesthesia.

• Authors: B K Lawton, N J Brown, C S Reilly, Z L S Brookes
• Journal: British journal of anaesthesia (Br J Anaesth) Vol. 108 Issue 6 Pg. 929-35 (Jun 2012) ISSN: 1471-6771 [Electronic] England
• PMID: 22511481 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anesthetics, Intravenous
• Calcium Channel Blockers
• Calcium Channels, L-Type
• 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
• Propofol

Topics

• 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester (pharmacology)
• Anesthetics, Intravenous (pharmacology)
• Animals
• Blood Pressure (drug effects)
• Calcium Channel Blockers (pharmacology)
• Calcium Channels, L-Type (drug effects, physiology)
• Dose-Response Relationship, Drug
• Hypertension (physiopathology)
• Male
• Microvessels (drug effects, physiology)
• Propofol (pharmacology)
• Rats
• Rats, Inbred SHR
• Rats, Inbred WKY
• Splanchnic Circulation (drug effects)