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Altering plasma volume, plasma osmolality, and the renin‐angiotensin system reduces the vascular responses to a pharmacological stress in conscious rats
Author(s) -
Loth Annemarie Katherine,
Willingham Laura A.,
Espenshied Megan R.,
Watanabe Mari A.,
Knuepfer Mark M.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a516
Subject(s) - vasopressin , plasma osmolality , endocrinology , medicine , plasma renin activity , vascular resistance , renin–angiotensin system , hemodynamics , blood volume , chemistry , angiotensin ii , tonicity , blood pressure
Cocaine (5 mg/kg, iv) causes a pressor response that, in some rats (vascular responders, VR), is due to an increase in systemic vascular resistance (SVR), and in other rats (mixed responders, MR), is due to an increase in cardiac output (CO) and a small increase in SVR. Previously we found that VR have greater sympathetic responses to cocaine. We hypothesized that reducing plasma volume, raising plasma osmolality or stimulating the renin‐angiotensin system (RAS) reduces vascular responses to cocaine. Furosemide (10 mg/kg sc, 60 min prior to cocaine) reduced both the decrease in CO and the rise in SVR in VR to cocaine making them no different than MR. Hypertonic NaCl (HS, 1 ml/kg, 5% sc, 10 min prior to cocaine) reduced the pressor response and prevented the increase in CO for MR but did not affect their SVR. HS attenuated both the decrease in CO and the increase in SVR in VR making the hemodynamic responses to cocaine in VR no different than those in MR. Isoproterenol (0.5 × 10‐6 M sc, 10 min prior to cocaine) diminished the increase in SVR and the decrease in CO in VR such that they were no different from MR. These data suggest that the greater vascular responsiveness to cocaine in VR is selectively attenuated by reduced plasma volume, plasma osmolality and the RAS. Since these stimuli increase vasopressin release we suggest that the greater vascular and sympathetic responses in VR may be inhibited by vasopressin. Supported by USPHS DA13256.