Reduced Membrane-Bound Catechol-O-Methyltransferase in the Liver of Spontaneously Hypertensive Rats

Abstract

We have previously reported that methylation of catecholamines by catechol-O-methyltransferase (COMT)washighly sensitive method to measure NE and NMN (7-9). Using this method, we demonstrated that methylation of catecholamines by COMT in SHR was attenuated during acute hypotension, when compared to that in WKY rats. Furthermore, intravenous administration of S-adenosyl-L-methionine (SAMe), a coenzyme for COMT, lowered blood pressure in SHR with a concomitant increase of NMN (10).Since COMTs exist in most tissues in a soluble form (S-COMT) as well as a membrane-bound form (MB-COMT), it is important to examine whether one of these subtypes plays a more crucial role than the other in the inactivation of released NE. Therefore, we determined S-and MB-COMT enzyme activities and the amount of protein in two representative rat tissues-the liver and kidney-as well as in erythrocytes. To examine the correlation between these enzymes and hypertensive states, pre-hypertensive SHR (4 weeks of age), hypertensive adult SHR (23 weeks of age), and agematched normotensive WKY rats were used.

Decreased Expression of Catechol-O-Methyltransferase in the Renal Cortex of Malignant Spontaneously Hypertensive Rats

“…study confirmed those previous results. It was reported that COMT expression in the kidney in 23-week-old SHR rats was greater than that in control WKY rats (Tsunoda et al 2003). In our experiments, we found that early onset of brain stroke (around 11 weeks) was characteristic in M-SHRSP rats and the rats died of brain stroke at around 15 weeks.…”

“…Transcription of the COMT gene is controlled by two distinct promoters (Männistö and Kaakkola 1999). Polypeptide is translated from the shorter transcript, soluble COMT, whereas a longer mRNA from the P2 promoter encodes mainly membrane-bound COMT (MB-COMT) (Tsunoda et al 2003). The molecular mass of COMT detected by western blot analysis was 24 kDa, and this COMT was considered to be the soluble form of rat COMT.…”

Low Catechol-O-methyltransferase Activity in the Brain and Blood Pressure Regulation

“…[14][15][16] However, there is a difference in their magnitudes: MB-COMT activities were only 2-5 times lower than S-COMT activities in the brain but were 15-25 times lower in the liver and the kidney. Considering the results obtained in the difference of affinities for COMT described below, MB-COMT in the brain may play a more important role than other peripheral tissues.…”

Suppression of Catechol-O-Methyltransferase Activity through Blunting of .ALPHA.2-Adrenoceptor Can Explain Hypertension in Dahl Salt-Sensitive Rats

“…In our previous studies we found that both the activity and protein expression of MB-COMT were lower in the liver of spontaneously hypertensive rats (SHR) than in the liver of Wistar-Kyoto (WKY) rats ( 11 ). We hypothesized that this reduced activity of MB-COMT is involved in the development of hypertension by increasing the local NE content.…”