Response of the rat mesenteric vasculature to chronic treatment with nitrendipine alone and in combination with atenolol: evidence of a significant drug interaction.
1. Nitrendipine 3 mg kg-1 was administered alone and in combination with atenolol 50 mg mg-1 day for 21 days to male normotensive Wistar rats and to spontaneously hypertensive Japanese Okamoto rats. Blood pressure was monitored daily. 2. Systolic blood pressure was decreased in normotensive Wistars and SHRs by nitrendipine alone and in combination. In both cases the decrease was greater in the hypertensive animal. There was no evidence of the combination having an additive hypotensive effect. 3. Following treatment, the response to exogenous noradrenaline (NA) and periarterial nerve stimulation (PNS) was measured in the in situ blood perfused mesentery. 4. Treatment with nitrendipine and the combination reduced the response to exogenous noradrenaline; with both, the reduction was greater in the hypertensive animal. The combination produced a larger reduction in response than nitrendipine alone. 5. Treatment with nitrendipine alone reduced the response to PNS in both normotensive and hypertensive animals, although this effect was greater in the SHR. 6. Combination treatment failed to change the response to electrical stimulation in the SHR, while in the normotensive rat it resulted in a large increase in response to higher frequency (16 and 35 Hz) stimulation. 7. As nitrendipine given alone reduced the response to PNS, and as we have previously shown a similar effect with atenolol given alone (Draper, Kingsbury, Redfern & Todd, 1992), the effect of the combination of nitrendipine and atenolol on responses to PNS is apparently influenced by some interaction between the two drugs.(ABSTRACT TRUNCATED AT 250 WORDS)
Draper
A J
AJ
Pharmacology Group, School of Pharmacy & Pharmacology, University of Bath, UK.
Kingsbury
M P
MP
Redfern
P H
PH
Todd
M H
MH
D000818:Animals; D001262:Atenolol / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004347:Drug Interactions; D004558:Electric Stimulation; D006973:Hypertension / Q000188:drug therapy; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D009568:Nitrendipine / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D013997:Time Factors
D001262:Atenolol; D009568:Nitrendipine; D009638:Norepinephrine