Biomedical subjects

C A Hamilton

Publications and source records attributed to C A Hamilton.

166 records · Page 10Linked to original sources

PubMedDate not supplied

The effect of aging on alpha-adrenoceptors and their responses in rabbits.

The effects of age on alpha-adrenoceptor responses, sensitivity and number were studied in rabbits aged from 1 to 36 months. Three types of investigation were carried out: conscious animal studies, isolated tissue studies and radioligand binding studies. Specific [3H]-prazosin binding decreased with age in both spleen and heart suggesting that the number of alpha 1-receptors declined at least in the tissues studied. The specific binding of [3H]-clonidine to spleen membranes and [3H]-yohimbine to platelets was not affected by age. In vitro responsiveness to alpha-adrenoceptor agonists decreased with age in abdominal aorta and renal artery, while the affinity of adrenoceptors for prazosin (pA2) was not altered. The decrease may be non-specific as responses to potassium were also altered. No change in alpha 2-adrenoceptor mediated platelet aggregation was observed. No change in pressor or depressor responses to full adrenoceptor agonists or to antagonists was observed in vivo. However, responses to clonidine, which is a partial agonist at alpha 1-adrenoceptors, were decreased. While aging influenced alpha-adrenoceptor subtypes differently, there was no direct relation between functional changes and number of receptors.

Aging↗

PubMedDate not supplied

Changes in plasma norepinephrine, blood pressure and heart rate during physical activity in hypertensive man.

We have investigated the changes in plasma norepinephrine and blood pressure and heart rate during a range of physical activities in eight hypertensive subjects in order to determine whether changes in plasma norepinephrine reflect changes in sympathetic activity. Blood pressure was recorded over 24 hours from an intra-arterial cannula. Plasma norepinephrine, measured by a sensitive radioenzymatic method, increased progressively with increasing levels of physical activity. In each subject a statistically significant linear relationship was observed between the logarithm of plasma norepinephrine and systolic blood pressure. Analysis of variance showed that 66% of the variance of plasma norepinephrine was associated with changes in blood pressure and heart rate. These observations support the hypothesis that plasma norepinephrine reflects short-term changes in sympathetic activity. Use of the quantitative relationship described, in conjunction with measurements of norepinephrine metabolism, may help to determine the significance of increased levels of plasma norepinephrine observed in some hypertensive patients.

Adult↗

PubMedDate not supplied

Alpha adrenoceptors and autonomic mechanisms in perinephritis hypertension in the rabbit.

Increased pressor responses to norepinephrine and other pressor agents have been reported to occur in human essential hypertension and in several animal models of experimental hypertension. These increased responses might be related to the development of hypertension or could be a secondary consequence of the elevation in blood pressure. We have examined pressor responses to alpha-adrenoceptor agonists and to angiotensin II in male New Zealand White rabbits with perinephritic hypertension. Increased pressor responses were observed for the alpha 1 adrenoceptor agonist phenylephrine and the mixed alpha 1/alpha 2-adrenoceptor agonist norepinephrine but not for the alpha 2 adrenoceptor selective agonist guanabenz or angiotensin II. The increase occurred within 7 days of surgery and in some animals was observed when mean arterial pressure was not significantly elevated. It could not readily be attributed to intimal thickening or hypertrophy of the arterial wall, altered basal levels of norepinephrine or epinephrine, changes in norepinephrine clearance, beta-adrenoceptor interactions, or decreased baroreceptor sensitivity. However, the possibility that vascular hypertrophy and decreased baroreflex sensitivity may contribute to the increase at later times cannot be excluded. In all tissues examined, specific prazosin binding was decreased in the older animals and specific clonidine binding was decreased in forebrain. However, these changes were observed in both hypertensive and sham-operated animals and were probably age-related. We believe the increased response to alpha 1-adrenoceptor agonists may be related to changes at a postreceptor site in the coupling of receptor activation to smooth muscle contraction.

Angiotensin II↗

PubMedDate not supplied

Withdrawal reactions following cessation of central alpha-adrenergic receptor agonists.

Interruption of long-term treatment with alpha 2-adrenergic receptor agonists may be associated with reversal of their hemodynamic effects, clinical and biochemical evidence of increased peripheral sympathetic activity, and behavioral responses similar to those seen after narcotic or alcohol withdrawal. Reactions are most commonly observed after short-acting imidazoline drugs such as clonidine and tiamenidine. Reactions are less common after longer acting agents such as guanfacine. A new management approach to withdrawal has been evaluated, which uses a combination of alpha 1-blockade (prazosin) and cardioselective beta-blockade (atenolol) together with a benzodiazepine (chlordiazepoxide). Withdrawal reactions were not observed in eight patients in whom clonidine was withdrawn under cover of these agents. The mechanism of the withdrawal reaction may involve agonist-induced down regulation of alpha 2-adrenergic receptor affinity, number, or both. Experimental studies with the irreversible alpha-antagonist phenoxybenzamine on the turnover of alpha 2-receptors suggest that recovery of receptor number may be much slower in the brain than in the periphery.

Adrenergic alpha-Agonists↗