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There is strong support for the view that the ventricular myocardium has a laminar organization in which myocytes are grouped into branching layers separated by cleavage planes. However, understanding of the extent and functional implications of this architecture has been limited by the lack of a systematic three-dimensional description of the organization of myocytes and associated perimysial collagen. We imaged myocytes and collagen across the left ventricular wall at high resolution in seven normal rat hearts using extended volume confocal microscopy. We developed novel reconstruction and segmentation techniques necessary for the quantitative analysis of three-dimensional myocyte and perimysial collagen organization. The results confirm that perimysial collagen has an ordered arrangement and that it defines a laminar organization. Perimysial collagen is composed of three distinct forms: extensive meshwork on laminar surfaces, convoluted fibers connecting adjacent layers, and longitudinal cords. While myolaminae are the principal form of structural organization throughout most of the wall, they are not seen in the subepicardium, where perimysial collagen is present only as longitudinal cords. connective tissue; perimysium; myocardium; laminar architecture

The role of the angiotensin II type 2 ([AT.sub.2]) receptor in cardiac hypertrophy remains controversial. We studied the effects of [AT.sub.2] receptors on chronic pressure overload-induced cardiac hypertrophy in transgenic mice selectively overexpressing A[T.sub.2] receptors in ventricular myocytes. Left ventricular (LV) hypertrophy was induced by ascending aorta banding (AS). Transgenic mice overexpressing [AT.sub.2] ([AT.sub.2]TG-AS) and nontransgenic mice (NTG-AS) were studied after 70 days of aortic banding. Nonbanded NTG mice were used as controls. LV function was determined by catheterization via LV puncture and cardiac magnetic resonance imaging. LV myocyte diameter and interstitial collagen were determined by confocal microscopy. Atrial natriuretic polypeptide (ANP) and brain natriuretic peptide (BNP) were analyzed by Northern blot. Sarco(endo)plasmic reticulum [Ca.sup.2+]-ATPase (SERCA)2, inducible nitric oxide synthase (iNOS), endothelial NOS, ERK1/2, p70S6K, Src-homology 2 domain-containing protein tyrosine phosphatase-1, and protein serine/threonine phosphatase 2A were analyzed by Western blot. LV myocyte diameter and collagen were significantly reduced in [AT.sub.2]TG-AS compared with NTG-AS mice. LV anterior and posterior wall thickness were not different between [AT.sub.2]TG-AS and NTG-AS mice. LV systolic and diastolic dimensions were significantly higher in [AT.sub.2]TG-AS than in NTG-AS mice. LV systolic pressure and end-diastolic pressure were lower in [AT.sub.2]TG-AS than in NTG-AS mice. ANP, BNP, and SERCA2 were not different between [AT.sub.2]TG-AS and NTG-AS mice. Phospholamban (PLB) and the PLB-to-SERCA2 ratio were significantly higher in [AT.sub.2]TG-AS than in NTG-AS mice. iNOS was higher in [AT.sub.2]TG-AS than in NTG-AS mice but not significantly different. Our results indicate that [AT.sub.2] receptor overexpression modified the pathological hypertrophic response to aortic banding in transgenic mice. cardiomyocyte; angiotensin II type 2 receptor; gene expression; protein expression