Although a reduction in myocardial norepinephrine stores in cardiac hypertrophy and congestive failure is well documented, norepinephrine turnover has been inadequately studied in such hearts. We compared norepinephrine turnover in control and cardiomyopathic hamsters by following the decline in specific activity of myocardial norepinephrine after labeling with an intraperitoneal tracer dose of 3 H-norepinephrine. Adult myocardial norepinephrine concentrations were not attained until 4 weeks of age in both strains. There was no difference in the rate constant (K) for myocardial norepinephrine turnover (0.107 ± 0.004 hours" 1 vs. 0.100 ± 0.005 hours" 1 ) in the two strains of hamsters during the neonatal period. In young control hamsters, K fell to 0.064 ± 0.004 hours" 1 , but that for age-matched hamsters with mild cardiac hypertrophy was 0.102 ± 0.001 hours" 1 (P < 0.001). There was little change in K as control hamsters aged. With the development of more severe hypertrophy in cardiomyopathic hamsters, cardiac norepinephrine decreased and resting K rapidly increased to approach the value obtained when hamsters were subjected to immobilization stress (0.302 ± 0.013 hours" 1 ). The maximum achievable K remained the same for both control and dystrophic hamsters even during terminal disease. Prolonged immobilization led to a reduction in cardiac norepinephrine in both strains. Ganglionic blockade of failing hamsters completely restored the levels of both cardiac norepinephrine and K to control values. Splenic noradrenergic nerves showed no change in K, norepinephrine content, or maximum K during cardiac decompensation. We conclude that, in the late stages of hamster cardiomyopathy, there is a progressive and possibly specific increase in cardiac sympathetic tone which leads to a concomitant decrease in cardiac norepinephrine. With the loss of sympathetic reserve, congestive failure supervenes.• The normal heart is richly supplied with noradrenergic sympathetic nerves. This innervation contributes little to intrinsic myocardial function (1) but is a most important mechanism for the elevation of cardiac output in response to a physiological stress such as exercise (2). In the absence of a catecholamine stimulus, cardiac output can be increased solely by the Frank-Starling mechanism (3). Dilated or noncompliant hearts, however, cannot take further advantage of the length-tension relationship and thus depend on sympathetic support to maintain cardiac output (4). This paper won the Young Investigators' Award given by the Canadian Cardiovascular Society.Dr. Sole was a Hunter Fellow of the Ontario Heart Foundation.Please address reprint requests to Dr. Michael J. Sole, Clinical Sciences Division, Medical Sciences Building, University of Toronto, Toronto, Canada M5S 1A8.Received May 1, 1975. Accepted for publication October 2, 1975.Circulation Research, Vol. 37, December 1975 There is considerable evidence for sympathetic dysfunction in the hearts of humans with congestive heart failure and animals with experime...
Sera from inbred rabbit strains have been studied to determine radio\x=req-\ thyroxine distribution after electrophoresis, to measure protein binding capacity for thyroxine (T4) and to examine possible interrelationships of binding capacity and serum protein-bound iodine (PBI). In electrophoretic studies at pH 7\m=.\4, serum albumin and prealbumin, the latter a previously unrecognized carrier of T4 in the rabbit, are the principal transport proteins. At pH 9\m=.\0,prealbumin is the major carrier (61 % of tracer). Prealbumin also binds significant quantities of tri-iodothyronine. The mean binding capacity of serum prealbumin for T4 in 12 rabbit strains was 500 \g=m\g/100 ml.Protein-bound iodine levels are known to be strain-dependent in the rabbit. In the current studies, however, there was no strain-specificity of prealbumin binding capacity, and no correlation between PBI and binding capacity of prealbumin, the principal T4-specific transport protein. These observations suggest that factors other than the capacity of binding proteins for T4 may be primary determinants of hormone levels (PBI) in blood in the rabbit.
While studies have been undertaken to define the various interactions between growth hormone (GH) levels and other hormones (14), the possibility of interaction between genetic factors and GH levels-analogous to the example of rabbit strain and serum PBI (5)-has not been systematically tested. Growth hormone level as a function of species has been reported in rats (6) and mice (7). In this report we show that, in the rabbit, strain significantly affects GH level.Materials and Methods. Animals and sera. Rabbits were healthy adults representing the inbred and incipient inbred strains maintained at the Jackson Laboratory on commercial laboratory chow (Purina Rabbit Chow Checkers 20% protein). Ten males and 10 females were chosen randomly for study from each of 12 strains. A vacuum-type bleeder (8) was used to bleed animals from marginal ear veins. Animals were bled between 9 AM and noon to minimize possible contribution of diurnal variation in parameters such as the PBI (9). One male and one female from each strain were bled each day and the order of bleeding was randomized within each day. Bleeding was carried out within a 2-week period. Thirty to 35 cm3 of blood was taken, allowed to clot at room temperature for approximately 30 min, and then under refrigeration centrifuged for 15 min. Serum was removed, divided into aliquots and stored at -20" until analyzed. In addition to these samples, sera from noninbred rabbits, previously immunized with human thyroidal microsomes, were kindly provided by Dr. David Solomon. Aliquots from these same serum samples had been assayed for serum iron and bilirubin levels (10) and serum PBI, thyroxine-binding prealbumin and dialyzable fraction thyroxine (1 1).Plasma growth hormone (GH). GH was measured by a double-antibody radioimmunoassay as previously described (7). Rat growth hormone for radioiodination (Rat-GH-I-1)2, rat growth hormone reference preparation (Rat-GH-RP-1, with a biological potency of 0.6 IU bovine GH/mg) and monkey anti-rat GH serum (A-Rat GHS-I ) were used in these studies. Plasma samples from individual rabbits were assayed in duplicate at each of two different volumes (50 and 100 pl), and the mean GH concentration of the four determinations was used for each estimate. Sensitivity of the assay was such that 0.2 ng GH could be detected. Plasma samples were stored at -20" until assayed. Plasmas were run randomly in four separate assays. Aliquots of pooled rat plasma were run in each assay and the GH concentrations determined on these aliquots were 35.7, 34.2, 34.5 and 34.8 ng/ml, respectively.Statistical methods. Strain data were analyzed * All rat growth hormone reagents used in these studies were kindly supplied by the National Institute of Arthritis and Metabolic Diseases Rat Pituitary Hormone Program. 820
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.