Effects of aging and antihypertensive treatment on aortic internal diameter in spontaneously hypertensive rats.
The effect of antihypertensive treatment on the development of large-artery remodeling in young animals has been widely studied, but reversal of established changes in older hypertensive animals has been largely ignored, although the latter represents a better paradigm for the human condition. We studied the effect of treatment with captopril plus hydrochlorothiazide, from 3 months onward, on geometry and wall stress of the thoracic aorta of adult (9 months, maturation) and old (15 months, senescence) spontaneously hypertensive rats; normotensive Wistar-Kyoto rats were used as controls. At 3 months of age, blood pressure, medial cross-sectional area, and internal diameter were higher in spontaneously hypertensive rats than in Wistar-Kyoto rats. In both strains, medial cross-sectional area and lumen diameter increased during maturation; there was little change with senescence. Changes in blood pressure were minor. Because medial hypertrophy failed to compensate for the wider lumen and higher intraluminal pressure in spontaneously hypertensive rats, medial stress was higher in these rats than in Wistar-Kyoto rats. Captopril plus hydrochlorothiazide rapidly lowered blood pressure and medial cross-sectional area. Despite a marked fall in blood pressure, the internal diameter of the thoracic aorta of treated animals was similar to that of untreated animals after 6 months of treatment and started to fall only after the animals had been treated for 1 year. Thus, under treatment with captopril plus hydrochlorothiazide, medial stress remained elevated, even after very-long-term treatment, because medial cross-sectional area was not adapted to internal diameter. We suggest that some changes in large-artery structure associated with hypertension and aging, such as the increase in diameter, take considerable time to regress after blood pressure is lowered, and this may explain why, despite treatment, wall stress remains elevated.
Giummelly
P
P
Laboratoire de Pharmacologie Cardiovasculaire, Faculté de Pharmacie, Henri Poincaré University-Nancy 1, Nancy, France.
Lartaud-Idjouadiene
I
I
Marque
V
V
Niederhoffer
N
N
Chillon
J M
JM
Capdeville-Atkinson
C
C
Atkinson
J
J
D000367:Age Factors; D000375:Aging; D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001013:Aorta, Thoracic / Q000187:drug effects / Q000473:pathology*; D001794:Blood Pressure; D002216:Captopril / Q000008:administration & dosage / Q000627:therapeutic use*; D004232:Diuretics; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology*; D006984:Hypertrophy; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D049993:Sodium Chloride Symporter Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D004232:Diuretics; D049993:Sodium Chloride Symporter Inhibitors; D006852:Hydrochlorothiazide; D002216:Captopril