Differential cerebrovascular responsiveness in spontaneously hypertensive rats following antihypertensive treatment with clonidine and verapamil.
Numerous studies have been reported examining the effects of antihypertensive treatment on peripheral vascular responsiveness in spontaneously hypertensive rats (SHR). This study was conducted to determine the effects of chronic treatment with 2 antihypertensive agents on cerebrovascular responsiveness in male SHR and Wistar-Kyoto (WKY) rats. SHR and WKY (3-4 weeks old) received either placebo, clonidine (CLON, 10 mg pellet) or verapamil (VER, 5 mg pellet). Vascular reactivity studies on the basilar artery, using standard smooth muscle bath techniques, were conducted following 6 weeks of treatment. Both CLON and VER significantly attenuated the rise in blood pressure in SHR. Basilar artery responsiveness to KCl, serotonin (5-HT), and calcium were significantly increased whereas responses to acetylcholine (ACH), isoproterenol (ISO) and sodium nitroprusside (SNP) were significantly reduced in SHR compared to WKY. CLON had no effect on basilar artery responsiveness to either the contractile or relaxation agents in SHR. However, although responses to KCl, 5-HT and calcium were not affected by VER in SHR, VER significantly increased the responses to ACH, ISO and SNP. Neither CLON nor VER treatment affected basilar artery responsiveness to any of the agents in WKY. These data demonstrate that, even though CLON and VER have similar antihypertensive effects, differential effects of the 2 agents on cerebrovascular responsiveness in the SHR are apparent. This would suggest that the vascular effects of VER and CLON are dependent upon the mechanism of action of the agents and not simply due to prevention of the elevation in blood pressure.
Soltis
E E
EE
Division of Pharmacology and Experimental Therapeutics, College of Pharmacy, University of Kentucky, Lexington 40536-0082.
Newman
P S
PS
Trowbridge
J L
JL
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology*
D014700:Verapamil; D003000:Clonidine