Postural hypotension following N-type Ca2+ channel blockade is amplified in experimental hypertension.

Abstract

OBJECTIVE:

To determine the relative importance of the cardiac and vascular sympathetic components of the orthostatic response to 90 degrees head-up tilt after N-type calcium-channel blockade in normotensive (sham renal cellophane wrap) and hypertensive (renal wrap) conscious rabbits.

METHODS:

The effects of N-type calcium-channel blockade with omega-conotoxin GVIA (omega-CTX, 10 microg/kg i.v. bolus) were assessed in the absence or presence of cardiac block by propranolol and methscopolamine. These were contrasted with the effects of alpha1-adrenoceptor antagonism (prazosin 0.5 mg/kg i.v. bolus, in the presence of cardiac block) or ganglion blockade (mecamylamine 4 mg/kg i.v. bolus).

RESULTS:

In vehicle (0.9% saline) treatment groups, the response to tilt consisted of a small pressor effect (4 +/- 2 and 7 +/- 1 mmHg) and tachycardia (29 +/- 6 and 17 +/- 6 beats/min) in sham (n = 6) and wrap (n = 5) rabbits, respectively. After prazosin administration (with cardiac block), there were significant falls in MAP of 3 +/- 1 and 7 +/- 2 mmHg in sham (n = 7) and wrap (n = 6) rabbits, respectively, in response to tilt omega-CTX caused postural hypotensive responses of 8 +/- 2 and 13 +/- 2 mmHg in sham (n = 6) and wrap (n = 7) rabbits, respectively, and 7 +/- 1 and 14 +/- 2 mmHg in sham (n = 7) and wrap (n = 7) rabbits with prior cardiac block. Similarly, mecamylamine caused falls in MAP of 8 +/- 1 and 10 +/- 2 mmHg in response to tilt in sham (n = 6) and wrap (n = 9) animals, respectively.

CONCLUSION:

Sympathetic vasoconstrictor effectors are primarily responsible for maintaining blood pressure during tilt in conscious rabbits. The postural hypotension caused by sympatholytic agents is about double in hypertensive rabbits, and N-type calcium-channel blockade is as effective as ganglion blockade at inducing this syndrome.

• Authors: C E Wright, A L Hawkes, J A Angus
• Journal: Journal of hypertension (J Hypertens) Vol. 18 Issue 1 Pg. 65-73 (Jan 2000) ISSN: 0263-6352 [Print] England
• PMID: 10678545 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenergic alpha-Agonists
• Adrenergic beta-Agonists
• Calcium Channel Blockers
• Calcium Channels, N-Type
• omega-Conotoxin GVIA
• Methoxamine
• Isoproterenol

Topics

• Adrenergic alpha-Agonists (pharmacology)
• Adrenergic beta-Agonists (pharmacology)
• Animals
• Blood Pressure (drug effects)
• Calcium Channel Blockers (pharmacology)
• Calcium Channels, N-Type (drug effects, metabolism)
• Female
• Heart Rate (drug effects)
• Hypertension (physiopathology)
• Hypotension, Orthostatic (etiology, physiopathology)
• Isoproterenol (pharmacology)
• Methoxamine (pharmacology)
• Nasopharynx (physiopathology)
• Rabbits
• Reflex (drug effects)
• omega-Conotoxin GVIA (pharmacology)