Single-Vesicle Catecholamine Release Has Greater Quantal Content and Faster Kinetics in Chromaffin Cells from Hypertensive, as Compared with Normotensive, Rats

• Published in: The Journal of pharmacology and experimental therapeutics 2008-02, Vol.324 (2), p.685-693
• Main Authors: Regiane Miranda-Ferreira, Ricardo de Pascual, Antonio M. G. de Diego, Afonso Caricati-Neto, Luis Gandía, Aron Jurkiewicz, Antonio G. García
• Format: Article
• Language: English
• Subjects: Action Potentials - physiology; Animals; Blood Pressure - physiology; Catecholamines - pharmacokinetics; Catecholamines - secretion; Chromaffin Cells - metabolism; Chromaffin Cells - secretion; Exocytosis - physiology; Hypertension - metabolism; Male; Rats; Rats, Inbred SHR; Rats, Sprague-Dawley; Secretory Vesicles - metabolism; Secretory Vesicles - secretion
• ISSN: 0022-3565; 1521-0103
• DOI: 10.1124/jpet.107.128819

In a previous study performed in the intact adrenal gland ( Lim et al., 2002 ), stimulation with acetylcholine (ACh) or high K + concentrations (K + ) produced greater catecholamine release in spontaneously hypertensive rats (SHR), as compared with normotensive animals. In this study, the time course of secretion was in the range of minutes. Hence, we do not know whether enhanced release is due to greater quantal content and/or distinct kinetics in SHRs and control animals. To get insight into the mechanism involved in such enhanced catecholamine secretory responses, we performed a single-vesicle release study in primary cultures of adrenal chromaffin cells, recorded with amperometry. Cells were stimulated with 2-s pulses of 1 mM ACh or 70 mM K + . The secretory responses to ACh or K + pulses in SHR cells as compared with control cells had the following characteristics: 1) double number of secretory events, 2) 4-fold augmentation of total secretion, 3) cumulative secretion that saturated slowly, 4) 3-fold higher complex events with two to four superimposed spikes that may be explained by faster spike kinetics, 5) about 2- to 3-fold higher event frequency at earlier post stimulation periods, and 6) 2- to 5-fold higher quantal content of simple spikes. We conclude that SHR cells have faster and larger catecholamine release responses, explained by more vesicles ready to undergo exocytosis and greater quantal content of vesicles. This could have relevance to further understand the pathogenic mechanisms involved in the development of high blood pressure, as well as in the identification of new drug targets to treat hypertension.