Coronary blood flow in senescent rats with late-onset hypertension.

We tested the hypothesis that the imposition of hypertension late in life would markedly limit maximal myocardial perfusion (MP). Young adult (8 mo) and senescent (24 mo) Fischer 344 rats were studied 3 mo after one-kidney, figure-8 renal wrap hypertension (RH) was induced. Sham-operated rats served as controls (Con). Regional MP was determined with radioactive microspheres in conscious rats before and during maximal coronary vasodilation with infusion of dipyridamole. Systolic arterial pressure (SAP) was significantly elevated in both RH age groups during weeks 2-6 following surgery and then fell to normotensive levels. After 3 mo SAP (mmHg) was significantly lower in the senescent RH rats (125 +/- 5) compared with their controls (147 +/- 3). In senescent RH rats left ventricular (LV) end-diastolic pressure increased fivefold. LV mass increased with age but not with treatment. LV minimal coronary vascular resistance (MCVR, mmHg.ml-1.min-100 g) increased significantly both with age and treatment (8 mo: Con = 0.07 +/- 0.01, RH = 0.14 +/- 0.01; 24 mo: Con = 0.11 +/- 0.01, RH 0.17 +/- 0.02). Treatment affected similar changes in the right ventricular MCVR. LV endocardial-to-epicardial perfusion ratio during rest was lower in the senescent groups but was not altered by hypertension. These data indicate that 1) both aging and this model of hypertension compromise maximal coronary perfusion and reserve in Fischer 344 rats, and 2) aging is associated with an increase in coronary vascular resistance in both ventricles at rest and in a relative reduction in maximal endocardial perfusion in the left ventricle.

Late onset renal hypertension in old rats alters left ventricular structure and function.

This study was designed to test the hypothesis that the left ventricle of the senescent rat has a limited compensatory response to late onset hypertension. Data were obtained from middle-aged (15 mo) and senescent (24 mo) Sprague-Dawley rats either 1 or 3 mo after the initiation of one-kidney figure-8 renal wrap (Grollman) hypertension. Peak left ventricular (LV) function assessed during acute volume expansion was not markedly affected 1 mo after induction of hypertension with the exception of a decrement in the acceleration of aortic flow (dF/dt) in the senescent hypertensive group. Three months after the surgery was performed, peak LV function (stroke index, stroke volume/g LV, and dF/dt) was depressed in the senescent hypertensive rats, compared with the controls. In contrast, these indexes in the 15-mo-old rats were similar in the experimental and control groups after either 1 or 3 mo of hypertension. Developed pressure, however, was not compromised by hypertension at either age. Cardiocyte hypertrophy due to pressure overload occurred in both age groups but to a greater extent in the senescent group. This cellular response did not cause an absolute increase in LV mass and was associated with endomyocardial foci of cellular degeneration and fibrosis suggestive of cell loss. Mitochondria-to-myofibril volume ratios were not significantly altered in the experimental groups at either age, thus the cellular hypertrophy in these rats was characterized by uniform organelle growth. These data support two important conclusions regarding late onset hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Remodeling of coronary vessels during aging in purebred beagles.

We compared six young (1 year) and six senescent (11 years) purebred beagles to determine the effects of aging on the coronary microvasculature. The hearts were perfusion-fixed in vitro, and myocardial specimens were subjected to microscopic image analysis. Absolute left ventricular mass increased by 55% with age, while cardiocyte cross-sectional area increased by 10% and 30% in the midmyocardium and endomyocardium, respectively. Although capillary numerical density was lower in the senescent dogs (16% in midmyocardium and 19% in endomyocardium), volume density was similar in the two groups because capillary diameter increased significantly with age in both regions. Capillary length density was reduced by 27% with age in the endomyocardium of the old beagles. Wall/lumen ratios of arterioles of three size classes (less than or equal to 15, 16-25, and 26-50 microns) were found to be nearly identical for the two age groups. Mean arteriolar diameter increased within the smallest size class in both ventricular regions. In contrast, a twofold or greater increase in wall thickness with age occurred in the left anterior descending coronary artery and its first branch, which was mainly due to expansion of the medial interstitium. The connective tissue fraction of the myocardium was significantly higher in the senescent than in the young in the epimyocardium and midmyocardium but not in the endomyocardium. These data provide evidence for three conclusions regarding aging of coronary vessels in beagles. First, a decline in capillary length density is limited to the endomyocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

Late-onset renal hypertension in old rats alters myocardial microvessels.

We tested the hypothesis that late-onset hypertension in middle-aged (15 mo) and senescent (24 mo) rats would adversely affect the coronary microvasculature. Morphometric analyses were performed on coronary capillaries and arterioles from rats with one-kidney, figure-8 renal wrap hypertension of 3-mo duration. Compared with control rats, wall-to-lumen ratios of arterioles with lumen diameters less than 25 microns were higher in the two hypertensive groups by approximately 30%; larger arterioles did not show consistent intergroup differences. A comparison of the two control groups revealed that wall-to-lumen ratio of arterioles with lumen diameters less than 50 microns tended to be greater in the senescent rats. Capillary numerical density was markedly reduced in the hypertensive animals of both age groups and caused an increase in the mean Krough cylinder radius and in the mean capillary domain. The latter increased by 28-63%; the largest increment occurred in the endomyocardium of the senescent group. A trend toward increased heterogeneity of capillary spacing was also noted in the hypertensive rats. The observed microvascular alterations occurred in the absence of an absolute increase in left ventricular mass but in the presence of cardiocyte hypertrophy. Thus the decrements in capillary numerical density are not only due to inadequate growth but reflect an absolute reduction in the number of these vessels associated with cardiocyte loss. It is concluded that late-onset hypertension in middle-aged and senescent rats is characterized by left ventricular wall remodeling that includes microvascular alterations that would be expected to limit maximal myocardial flow and O2 supply to the cardiocyte.