Effects of DC-015, a novel potent and selective α1-adrenoceptor antagonist on plasma lipid and vascular reactivity in hyperlipidaemic rats

Joen Rong Sheu, I. Hsun Peng, Yen Mei Lee, Mao Hsiung Yen

Research output: Contribution to journalArticle

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Abstract

The effects of DC-015, a newly synthesized quinazoline derivative, on plasma lipids, lipoprotein levels and vascular reactivity were investigated in Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). The hypotensive effect of DC-015 was compared with prazosin in SHR. Intravenous administration of DC-015 and prazosin (both at 0.01, 0.05 and 0.1 mg/kg) induced dose-dependent reductions in mean arterial pressure (MAP) which reached a maximal effect 5 min after injection and persisted over 2 h in SHR. DC-015 decreased MAP with equal efficiency compared with prazosin. The plasma levels of total cholesterol (CE), low-density lipoprotein (LDL)-CE and total triglyceride (TG) were markedly increased and the levels of high-density lipoprotein (HDL)-CE were markedly decreased in both high fat-high cholesterol (HF-HC) diet fed WKY and SHR. In HF-HC diet fed WKY and SHR, the total plasma CE, LDL-CE and total plasma TG were significantly reduced after oral administration of DC-015 (1 mg/kg, twice a day) for 4 weeks. Furthermore, DC-015 therapy was associated with increased HDL-CE levels and thus the ratio of total CE to HDL-CE was improved. The antihyperlipidaemic effect of prazosin was less than that of DC-015. Significantly attenuated median effective concentration (EC50) values and augmented maximal responses for phenylephrine-induced contraction of aortic rings were observed in HF-HC diet fed WKY and SHR. Endothelium-dependent relaxation to acetylcholine was impaired while endothelium-independent relaxation to nitroglycerin was well preserved. Oral administration of DC-015 (1 mg/kg, twice a day) for 4 weeks significantly augmented EC50 values and attenuated maximal responses for phenylephrine-induced contraction of aortic rings in HF-HC diet fed WKY and SHR. Prazosin (1 mg/kg, twice a day) showed a lesser extent of efficiency than DC-015 at normalization of vasorelaxation in HF-HC diet fed WKY aud SHR. It is concluded that DC-015, a potent antihypertensive agent, may have additional advantage in also reducing hyperlipidaemia.

Original languageEnglish
Pages (from-to)207-213
Number of pages7
JournalClinical and Experimental Pharmacology and Physiology
Volume23
Issue number3
Publication statusPublished - 1996

Fingerprint

Adrenergic Receptors
Blood Vessels
Inbred SHR Rats
Inbred WKY Rats
Lipids
Cholesterol
Prazosin
High Fat Diet
HDL Cholesterol
Phenylephrine
LDL Cholesterol
Endothelium
Oral Administration
Arterial Pressure
Triglycerides
DC 015
Quinazolines
Hypolipidemic Agents
Nitroglycerin
Hyperlipidemias

Keywords

  • α-adrenoceptor antagonist
  • DC-015
  • hyperlipidaemia
  • spontaneously hypertensive rats
  • Wistar-Kyoto rats

ASJC Scopus subject areas

  • Physiology
  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Effects of DC-015, a novel potent and selective α1-adrenoceptor antagonist on plasma lipid and vascular reactivity in hyperlipidaemic rats. / Sheu, Joen Rong; Peng, I. Hsun; Lee, Yen Mei; Yen, Mao Hsiung.

In: Clinical and Experimental Pharmacology and Physiology, Vol. 23, No. 3, 1996, p. 207-213.

Research output: Contribution to journalArticle

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T1 - Effects of DC-015, a novel potent and selective α1-adrenoceptor antagonist on plasma lipid and vascular reactivity in hyperlipidaemic rats

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AU - Peng, I. Hsun

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AU - Yen, Mao Hsiung

PY - 1996

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AB - The effects of DC-015, a newly synthesized quinazoline derivative, on plasma lipids, lipoprotein levels and vascular reactivity were investigated in Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). The hypotensive effect of DC-015 was compared with prazosin in SHR. Intravenous administration of DC-015 and prazosin (both at 0.01, 0.05 and 0.1 mg/kg) induced dose-dependent reductions in mean arterial pressure (MAP) which reached a maximal effect 5 min after injection and persisted over 2 h in SHR. DC-015 decreased MAP with equal efficiency compared with prazosin. The plasma levels of total cholesterol (CE), low-density lipoprotein (LDL)-CE and total triglyceride (TG) were markedly increased and the levels of high-density lipoprotein (HDL)-CE were markedly decreased in both high fat-high cholesterol (HF-HC) diet fed WKY and SHR. In HF-HC diet fed WKY and SHR, the total plasma CE, LDL-CE and total plasma TG were significantly reduced after oral administration of DC-015 (1 mg/kg, twice a day) for 4 weeks. Furthermore, DC-015 therapy was associated with increased HDL-CE levels and thus the ratio of total CE to HDL-CE was improved. The antihyperlipidaemic effect of prazosin was less than that of DC-015. Significantly attenuated median effective concentration (EC50) values and augmented maximal responses for phenylephrine-induced contraction of aortic rings were observed in HF-HC diet fed WKY and SHR. Endothelium-dependent relaxation to acetylcholine was impaired while endothelium-independent relaxation to nitroglycerin was well preserved. Oral administration of DC-015 (1 mg/kg, twice a day) for 4 weeks significantly augmented EC50 values and attenuated maximal responses for phenylephrine-induced contraction of aortic rings in HF-HC diet fed WKY and SHR. Prazosin (1 mg/kg, twice a day) showed a lesser extent of efficiency than DC-015 at normalization of vasorelaxation in HF-HC diet fed WKY aud SHR. It is concluded that DC-015, a potent antihypertensive agent, may have additional advantage in also reducing hyperlipidaemia.

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