Role of L-type calcium channels in altered microvascular responses to propofol in hypertension.
Br J Anaesth
; 108(6): 929-35, 2012 Jun.
Article
em En
| MEDLINE
| ID: mdl-22511481
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Bloqueadores dos Canais de Cálcio
/
Propofol
/
Anestésicos Intravenosos
/
Canais de Cálcio Tipo L
/
Microvasos
/
Hipertensão
Limite:
Animals
Idioma:
En
Revista:
Br J Anaesth
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Reino Unido