Significance of the Vascular Concentration of Angiotensin II–Receptor Blockers on the Mechanism of Lowering Blood Pressure in Spontaneously Hypertensive Rats
To clarify the hypotensive mechanism of angiotensin II receptor–blockers (ARBs), drug concentrations in plasma and vascular tissues were measured using matrix-assisted laser desorption ionization time-of-flight mass spectrometry and imaging mass spectrometry. In spontaneously hypertensive rats, syst...
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| Format: | Article |
| Language: | English |
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Elsevier
2013-01-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319302385 |
| _version_ | 1818251304976252928 |
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| author | Shinji Takai Denan Jin Hiroshi Sakonjo Takayuki Takubo Toyofumi Nakanishi |
| author_facet | Shinji Takai Denan Jin Hiroshi Sakonjo Takayuki Takubo Toyofumi Nakanishi |
| author_sort | Shinji Takai |
| collection | DOAJ |
| description | To clarify the hypotensive mechanism of angiotensin II receptor–blockers (ARBs), drug concentrations in plasma and vascular tissues were measured using matrix-assisted laser desorption ionization time-of-flight mass spectrometry and imaging mass spectrometry. In spontaneously hypertensive rats, systolic blood pressure (SBP) was measured 2 and 24 h after administration of candesartan cilexetil (0.3, 1, or 3 mg/kg) or azilsartan (0.3, 1, or 3 mg/kg). SBP was similarly lowered 2 h after administration of azilsartan or candesartan cilexetil, but it was significantly lower in the azilsartan-treated group than in the candesartan cilexetil-treated group at 24 h. Angiotensin II–induced vascular contractions were similarly attenuated 2 h after administration of these drugs, and the contractions were significantly lower in the azilsartan-treated group at 24 h. Although plasma concentration was significantly lower in the azilsartan-treated group at 24 h, vascular concentration of azilsartan was significantly greater than that of candesartan. Significant correlations between SBP and vascular concentrations were observed both at 2 and 24 h, while no significant correlation was observed between plasma and vascular concentrations. In conclusion, the mechanism of ARB-induced hypotension is likely to depend on vascular concentrations rather than plasma concentrations. Keywords:: angiotensin II, angiotensin II receptor blocker, hypertension, imaging mass spectrometry, vascular contraction |
| first_indexed | 2024-12-12T16:06:10Z |
| format | Article |
| id | doaj.art-700b15ed977e411b81a81edf140f7735 |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-12T16:06:10Z |
| publishDate | 2013-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-700b15ed977e411b81a81edf140f77352022-12-22T00:19:17ZengElsevierJournal of Pharmacological Sciences1347-86132013-01-011234371379Significance of the Vascular Concentration of Angiotensin II–Receptor Blockers on the Mechanism of Lowering Blood Pressure in Spontaneously Hypertensive RatsShinji Takai0Denan Jin1Hiroshi Sakonjo2Takayuki Takubo3Toyofumi Nakanishi4Department of Pharmacology, Osaka Medical College, 2-7 Daigaku-cho, Takatsuki City, Osaka 569-8686, Japan; Corresponding author. pha010@art.osaka-med.ac.jpDepartment of Pharmacology, Osaka Medical College, 2-7 Daigaku-cho, Takatsuki City, Osaka 569-8686, JapanShiga Research Center, Nissei BILIS, 555 Minakuchi-cho, Shiga 528-0052, JapanDepartment of Clinical and Laboratory Medicine, Osaka Medical College, 2-7 Daigaku-cho, Takatsuki City, Osaka 569-8686, JapanDepartment of Clinical and Laboratory Medicine, Osaka Medical College, 2-7 Daigaku-cho, Takatsuki City, Osaka 569-8686, JapanTo clarify the hypotensive mechanism of angiotensin II receptor–blockers (ARBs), drug concentrations in plasma and vascular tissues were measured using matrix-assisted laser desorption ionization time-of-flight mass spectrometry and imaging mass spectrometry. In spontaneously hypertensive rats, systolic blood pressure (SBP) was measured 2 and 24 h after administration of candesartan cilexetil (0.3, 1, or 3 mg/kg) or azilsartan (0.3, 1, or 3 mg/kg). SBP was similarly lowered 2 h after administration of azilsartan or candesartan cilexetil, but it was significantly lower in the azilsartan-treated group than in the candesartan cilexetil-treated group at 24 h. Angiotensin II–induced vascular contractions were similarly attenuated 2 h after administration of these drugs, and the contractions were significantly lower in the azilsartan-treated group at 24 h. Although plasma concentration was significantly lower in the azilsartan-treated group at 24 h, vascular concentration of azilsartan was significantly greater than that of candesartan. Significant correlations between SBP and vascular concentrations were observed both at 2 and 24 h, while no significant correlation was observed between plasma and vascular concentrations. In conclusion, the mechanism of ARB-induced hypotension is likely to depend on vascular concentrations rather than plasma concentrations. Keywords:: angiotensin II, angiotensin II receptor blocker, hypertension, imaging mass spectrometry, vascular contractionhttp://www.sciencedirect.com/science/article/pii/S1347861319302385 |
| spellingShingle | Shinji Takai Denan Jin Hiroshi Sakonjo Takayuki Takubo Toyofumi Nakanishi Significance of the Vascular Concentration of Angiotensin II–Receptor Blockers on the Mechanism of Lowering Blood Pressure in Spontaneously Hypertensive Rats Journal of Pharmacological Sciences |
| title | Significance of the Vascular Concentration of Angiotensin II–Receptor Blockers on the Mechanism of Lowering Blood Pressure in Spontaneously Hypertensive Rats |
| title_full | Significance of the Vascular Concentration of Angiotensin II–Receptor Blockers on the Mechanism of Lowering Blood Pressure in Spontaneously Hypertensive Rats |
| title_fullStr | Significance of the Vascular Concentration of Angiotensin II–Receptor Blockers on the Mechanism of Lowering Blood Pressure in Spontaneously Hypertensive Rats |
| title_full_unstemmed | Significance of the Vascular Concentration of Angiotensin II–Receptor Blockers on the Mechanism of Lowering Blood Pressure in Spontaneously Hypertensive Rats |
| title_short | Significance of the Vascular Concentration of Angiotensin II–Receptor Blockers on the Mechanism of Lowering Blood Pressure in Spontaneously Hypertensive Rats |
| title_sort | significance of the vascular concentration of angiotensin ii receptor blockers on the mechanism of lowering blood pressure in spontaneously hypertensive rats |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319302385 |
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