Acute antihypertensive action of nitroxides in the spontaneously hypertensive rat
| Autor: | Christopher S. Wilcox, Yifan Chen, Stephanie Connors, James Mitchell, Kinjal Patel, William J. Welch, Jonathan Blau, Margaret M. Tarpey, Margarida Mendonca, Kathryn Dennehy, Murali Krishna |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Nitroxide mediated radical polymerization
Dose-Response Relationship Drug Molecular Structure biology Superoxide Dismutase Physiology Chemistry Pharmacology Rats Nitric oxide Cyclic N-Oxides Superoxide dismutase chemistry.chemical_compound Spontaneously hypertensive rat Blood pressure Biochemistry Heart Rate Rats Inbred SHR Physiology (medical) Hypertension Heart rate biology.protein Animals Antihypertensive Agents |
| Zdroj: | American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 290:R37-R43 |
| ISSN: | 1522-1490 0363-6119 |
| Popis: | Tempol is an amphipathic radical nitroxide (N) that acutely reduces blood pressure (BP) and heart rate (HR) in the spontaneously hypertensive rat (SHR). We investigated the hypothesis that the response to nitroxides is determined by SOD mimetic activity or lipophilicity. Groups ( n = 6–10) of anesthetized SHRs received graded intravenous doses of Ns: tempol (T), 4-amino-tempo (AT), 4-oxo-tempo (OT), 4-trimethylammonium-2,2,6,6-tetramethylpiperidine-1-oxyl iodide (CAT-1), 3-carbamoyl-proxyl (3-CP), or 3-carboxy-proxyl (3-CTPY). Others received native or liposomal (L) Cu/Zn SOD. T and OT are uncharged, AT is positively charged and cell-permeable, and CAT-1 is positively charged and cell-impermeable. 3-CP and 3-CTPY have five-member pyrrolidine rings, whereas T, AT, OT, and CAT-1 have six-member piperidine rings. T and AT reduced mean arterial pressure (MAP) similarly (−48 ± 2 mmHg and −55 ± 8 mmHg) but more ( P < 0.05) than OT and CAT-1. 3-CP and 3-CTPY were ineffective. The group mean change in MAP with piperidine Ns correlated with SOD activity ( r = −0.94), whereas their ED50correlated with lipophilicity ( r = 0.89). SOD and L-SOD did not lower BP acutely but reduced it after 90 min (−32 ± 5 and −31 ± 6 mmHg; P < 0.05 vs. vehicle). Pyrrolidine nitroxides are ineffective antihypertensive agents. The antihypertensive response to piperidine Ns is predicted by SOD mimetic action, and the sensitivity of response is by hydrophilicity. SOD exerts a delayed hypotensive action that is not enhanced by liposome encapsulation, suggesting it must diffuse to an extravascular site. |
| Databáze: | OpenAIRE |
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