Aggressive long-term antihypertensive therapy with pinacidil does not cause regression of cardiovascular hypertrophy in the spontaneously hypertensive rat.
After dosage titration from the age of 1 month to the age of 3 months, spontaneously hypertensive rats (SHR) were treated with pinacidil 10 mg/kg daily until the age of 6 or 12 months. Morphometric data were obtained from the treated SHR as well as from untreated age-matched SHR and normotensive Wistar-Kyoto rats (WKY) at these two developmental stages. Heart:body weight ratios and media:lumen ratios for resistance vessels were determined. Vessels obtained from the mesenteric region were investigated on a myograph. Vessels from heart, kidney and lung were investigated by morphometric analysis of histological sections, only specimens from 12-month-old rats were used. In SHR no effects of either ageing or treatment were detectable, although their blood pressure had been effectively held at normotensive levels throughout the life of the treated animals from the age of 3 months. With the exception of the media index of the pulmonary vessels, which was not statistically different from treated or control SHR, the WKY morphological parameters were significantly lower. In conclusion, pinacidil normalized blood pressure without complications, but this did not affect SHR cardiovascular structure. It is suggested that development of this strain-specific enlargement can only be modified if blood pressure is kept at hypotensive levels, or if the effect of a hitherto unidentified causative factor is antagonized by more-specific pharmacological treatment.
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000209:etiology / Q000517:prevention & control*; D006146:Guanidines / Q000627:therapeutic use*; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D008297:Male; D020110:Pinacidil; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
D000959:Antihypertensive Agents; D006146:Guanidines; D020110:Pinacidil