Immediate and prolonged hemodynamic effects of TA-3090 on spontaneously hypertensive (SHR) and normal Wistar-Kyoto (WKY) rats.
Systemic and regional hemodynamic effects of the new effects of the new calcium antagonist TA-3090, a benzothiazepine derivative that is similar to diltiazem, were studied both acutely (0.3 and 0.6 mg/kg IV) and chronically (30 mg/kg by once-daily gastric gavage for 3 weeks) in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. All hemodynamic data were obtained in the conscious state using the reference sample radiomicrospheres method. Mean arterial pressure was reduced significantly by both immediate and long-term treatment in both rat strains. Stroke index remained unchanged in each study group, but the heart rate of the SHR and WKY decreased and increased, respectively, with the higher dose in the intravenous aspect of this study. As a result, total peripheral resistance decreased significantly in all groups, normotensive or hypertensive, although this fall was not distributed uniformly throughout the body. Intrarenal hemodynamics revealed significant differences between SHR and WKY by prolonged treatment with TA-3090. Efferent as well as afferent glomerular arteriolar resistances decreased and therefore calculated glomerular capillary hydrostatic pressure decreased in SHR; however, efferent glomerular arteriolar resistance and glomerular pressure remained unchanged in WKY. By contrast, in the acute study, no such differences were obtained. Further, 3 weeks' treatment did not alter cardiac mass in either rat strain. Thus, TA-3090 decreased arterial pressure through a fall in total peripheral resistance without major cardiac effects in both rats strains. In contrast, the agent reduced vascular resistances only in the SHR; and this was achieved with dilation of both the afferent and efferent glomerular arterioles.(ABSTRACT TRUNCATED AT 250 WORDS)
Isshiki
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Division of Research, Alton Ochsner Medical Foundation, New Orleans, Louisiana 70121.
Pegram
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Frohlich
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D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D004110:Diltiazem / Q000031:analogs & derivatives*; D006439:Hemodynamics / Q000187:drug effects*; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013841:Thiazepines / Q000494:pharmacology*
D000959:Antihypertensive Agents; D013841:Thiazepines; C056595:clentiazem; D004110:Diltiazem