Effects of a new dihydropyridine derivative, CV-4093.2HCl, on renal hemodynamics in spontaneously hypertensive rats.
The effects of a new calcium antagonist, CV-4093.2HCl, on renal hemodynamics were examined in anesthetized and conscious spontaneously hypertensive rats (SHR). In the anesthetized rats, CV-4093.2HCl (5 and 10 micrograms/ kg, i.v.) showed a long-lasting hypotensive action, dilated renal vasculature, and increased renal blood flow. These renal hemodynamic actions of CV-4093.2HCl were more prominent than those of nicardipine (5 and 10 micrograms/kg). Moreover, CV-4093.2HCl (10 micrograms/kg, i.v.) inhibited renal vascular contractions induced by intravenous norepinephrine and angiotensin II. The inhibitory effect of CV-4093.2HCl was much more marked than that of nicardipine, although the inhibitory effects of both calcium antagonists on systemic pressor responses induced by the vasoactive substances were almost the same. In addition, CV-4093.2HCl (1 and 3 mg/kg, p.o.) increased blood flow in the kidneys but not in the other organs except for the small intestine in conscious SHR. These results suggest that CV-4093.2HCl has a relatively higher affinity for the renal vascular bed (renal resistance vessels), and its effect on renal hemodynamics seems to be beneficial for treating hypertension.
Nagaoka
A
A
Biology Laboratories, Central Research Division, Takeda Chemical Industries, Ltd., Osaka, Japan.
Shibota
M
M
Hamajo
K
K
D000758:Anesthesia; D000804:Angiotensin II / Q000037:antagonists & inhibitors; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D009529:Nicardipine / Q000494:pharmacology; D009578:Nitrobenzenes; D009638:Norepinephrine / Q000494:pharmacology; D010879:Piperazines; D051381:Rats; D011918:Rats, Inbred SHR; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects*; D013997:Time Factors
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009578:Nitrobenzenes; D010879:Piperazines; D000804:Angiotensin II; C054218:manidipine; D009529:Nicardipine; D009638:Norepinephrine