Effects of verapamil and carbon monoxide on blood pressure and heart mass in the spontaneously hypertensive rat.
Studies were carried out to examine the relationship between blood pressure lowering using the Ca2+ channel blocker verapamil, and regression of ventricular hypertrophy, in the spontaneously hypertensive rat (SHR). Untreated male SHR showed rapidly developing hypertension (systolic pressure 194 +/- 2 mm Hg, 109 days of age) and moderate ventricular hypertrophy. Verapamil (Calan-SR, G.D. Searle Co.) treatment for 30 days at maximum doses of 18.7 and 49.9 mg/kg per day supplied in the food, lowered blood pressure maximally 37 mm Hg. The drug had no effect on heart rate. Decrease in the mass of the left ventricle plus interventricular septum was positively correlated with the verapamil-induced decrease in blood pressure (r = 0.69, P less than 0.001). SHR exposed continuously to 500 ppm carbon monoxide (CO) for 30 days showed a similar decrease in blood pressure (33.0 mm Hg). Such SHR, however, displayed increases in mass of the left ventricle plus septum and right ventricle, and of hematocrit, nearly identical to same age Sprague-Dawley rats similarly exposed to CO. Neither verapamil nor CO treatment altered myocardial water content. The results suggest that a modest lowering of blood pressure with verapamil in the SHR produces a relatively rapid decrease in left ventricular mass. It also shows that even when afterload is reduced in the SHR, as with CO, substantial ventricular hypertrophy develops, probably because of augmented preload, and that it is comparable to that produced in non-hypertensive rats.
Penney
D G
DG
Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48201.
Robinson
M C
MC
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002248:Carbon Monoxide / Q000494:pharmacology*; D006332:Cardiomegaly / Q000139:chemically induced / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D014700:Verapamil / Q000494:pharmacology*
D002248:Carbon Monoxide; D014700:Verapamil